ENDOCRINOLOGY

CUSHING SYNDROME:

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ADRENAL INSUFFICIENCY

PRIMARY ADRENAL INSUFFICIENCY – Case:

[38yoF w/3 week h/o wt loss, nausea, abdominal pain, and postural dizziness. She traveled to Thailand
6 months ago and has felt fatigued since then. BP 90/60. Pharyngeal examination shows bilateral
tonsillar enlargement Skin examination shows increased pigmentation at the palmar creases and
mucous membranes as well as a few patches of vitiligo. Initial laboratory testing shows mild
hyponatremia and hyperkalemia with normal renal function. Complete blood count is normal, but
differential shows moderate eosinophilia Follow-up testing confirms a low 8 AM serum cortisol.]
Which of the following is the MOST LIKELY CAUSE OF THIS PATIENT'S ADRENAL INSUFFICIENCY?
= Autoimmune Adrenalitis

Educational objective:
 Case: Pt has Chronic Primary Adrenal Insufficiency PAI: (Weight loss, abdominal pain, and
fatigue. Hyperpigmentation dt cosecretion of Melanocyte stimulating hormone MSH
w/ACTH)….reflex↑ dt Cortisol deficiency/LOW. Aldosterone LOW → HoTN,
Hyponatremia LOW, Hyperkalemia HIGH. + Eosinophilia & hyperplasia of lymphoid tissues
(ex: Tonsils) = common but nonspecific

 Autoimmune adrenalitis = MCCO Primary Adrenal Insufficiency (PAl) in developed

countries. (90%)….Autoantibodies against Adrenal enzymes that are needed for Cortisol
synthesis
o Can be alone or associate with OTHER autoimmune sd (eg: Hypothyroid, Vitiligo)
 Key differentiating features of PAl from central adrenal insufficiency are
HYPERPIGMENTATION and HYPERKALEMIA seen in PAl.

WRONG:
 Bilateral Adrenal Hemorrhage dt SEPSIS (ex: N. Meningitidis) → PAI….but LESS COMMON +
ONSET ACUTE & dramatic
 “Exogenous Glucocorticoids” – Yes, can suppress pituitary ACTH secretion & Hypothalamic
secretion of CRH → Cortisol…. BUT MSH (Melanocyte Stimulating Hormone) is NOT
INCREASED….so don’t see Hyperpigmentation
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HYPERALDOSTERONISM
PRIMARY HYPERALDOSTERONE – Case: [55yoM f/u HTN. BP 157/95. Potassium 3.1; Plasma renin
activity: undetectable]
Which of the following best EXPLAINS patient’s Lab findings?
= Primary hyperaldosteronism

Why: HTN + Undetectable Renin activity = Primary Hyperaldosteronism

 Primary Hyperaldosterone → HTN [dt Adrenal Adenoma or Bilateral Adrenal Hyperplasia]

Educational objective: Primary hyperaldosteronism

 HTN, mild Hypernatremia elevated
 Hypokalemia, metabolic alkalosis, and LOW Renin activity [dt feedback inhibition]
 Hypokalemia is not always present at baseline but IF USE DIURETICS…can trigger
Symptomatic Hypokalemia. Clinically significant hypernatremia and edema are not seen
due to aldosterone escape.
  Hypokalemia & Hypertension w/Low Renin [Congenital adrenal hyperplasia, Cushing,
Exogenous mineralocorticoid intake]

Why WRONG:
ACE-I side effect
= decreases conversion of AT1
to ATII → Aldosterone
Decrease, and Renin Reflex
INCREASE
ACE-I → Hyperkalemia↑ &
Rise Creatinine (dt reduced
GFR)
Diuretic use (ex thiazide)
Diuretic use in absence of PH
cause:
*HYPOKALEMIA ↓K
*Renin reflex INCREASE
Unilateral renal stenosis:
*HTN, abdominal bruits,
episodes of flash pulmonary
edema(cough, crackles)
*cause Renin INCREASE →
Secondary Hyperaldosterone

PRIMARY HYPERALDOSTERONE – Case:

[45yoM follow-up elevated blood pressure and an incidental right adrenal mass on abdominal imaging
The patient has no prior abnormal findings. He has no symptoms except mild headache, which he
attributes to stress at work. BP today is 160/94 mm Hg. Serum potassium is 3.0 mEq/L and sodium is
146 mEq/L. Further workup shows a plasma aldosterone/plasma renin activity ratio of 45. He refuses to
undergo surgery for removal of the adrenal mass.]
Which of the following is the best initial therapy for this patient?
= Eplerenone
[HTN, Hypokalemia, CT scan see Adrenal Mass = Primary Hyperaldosteronism] & Aldo:Renin
ratio >20…… ELEVATED Aldo → Decreases Renin (feedback)

Educational objective:
 Primary hyperaldosteronism usually dt: adrenal adenoma or bilateral adrenal hyperplasia
 SURGERY is preferred for UNILATERAL ADRENAL ADENOMA. – but can’t do in this case, he
doesn’t want surgery…

 NEXT STEP INITIAL Drug option:

o Eplerenone: (selective aldosterone antagonist…fever side effects than
spironolactone)
o Spironolactone (AE: ↓libido, gynecomastia; breast tenderness, menstrual
irregularities) = aldosterone antagonist [recommended for = BILATERAL ADRENAL
HYPERPLASIA or with unilateral adrenal adenoma who either refuse surgery or are
poor surgical candidates.]

Why WRONG:
 Thiazides, ACE-I….. for BP control in These patients (NOT BEST INITIAL THERAPY]
PRIMARY HYPERALDOSTERONISM – CASE
[27yoM comes for f/u HTN. Two weeks ago, he was found to have high blood pressure during an
emergency department visit for a sports injury The patient has a strong family history of
hypertension and stroke. His blood pressure is 155/97 mm Hg and pulse is 78/min. Instructed to follow
a low-salt diet and started on low-dose (12 5 mg daily) hydrochlorothiazide Two weeks later, the
patient comes to the emergency department complaining of muscle cramps, weakness, and
palpitations. His blood pressure is 150/93 mm Hg and pulse is 82/min. Mucous membranes are moist
Laboratory results are as follows Potassium 2.5; Glucose 78mg; Creatinine 1.0mg]

Which of the following is the BEST NEXT STEP IN MANAGEMENT of this patient?

ED:
 YOUNG pt + family h/o HTN = Secondary cause of Hypertension)
 Earily induced hypokalemia after starting a thiazide suggests = Primary
Hyperaldosteronism… =Don’t have spontaneous hypokalemia….they are PRONE TO develop
DIURETIC-INDUCED HYPOKALEMIA
o Others: Metabolic ALKALOSIS & Mild Hypernatremia (143-147mEq)

 BEST SCREEN TEST/NEXT STEP:

o Early Morning Plasma Aldosterone Concentration (PAC) to Plasma RENIN ratio
 PAC/PRA ratio >20 with Plasma ALDOSTERONE > 15 = Primary
Hyperaldosteronism
NEUROBLASTOMA

PHEOCHORMOCYTOMA

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HYPOTHYROID
HYPOTHYROID – CASE:
[Hypothyroid clues + memory changes] Labs. ELEVATED TSH, decreased Free T4. Admiinistered
Levothyroxine improved her symptoms.]
What does she have?
= Hypothyroidism (likely Hashimoto)

ED:
 Hypothyroidism → cause REVERSIBLE changes in MEMORY & MENTAL STATUS

RADIOIODINE THERAPY SIDE EFFECT IN GRAVES’ – CASE

Which is MC side effect of Radioiodine therapy?
= Hypothyroidism

Educational Objective:
 Hypothyroidism is MC side effect of Radioiodine therapy, but it is easily treated with
levothyroxine therapy. The patient's eye disease may worsen at the beginning of
radioiodine therapy.

HASHIMOTO THYROIDITIS

PAINLESS THYROIDITIS (SILENT THYROIDITIS) –CASE:

[24yoF…..3 weeks after heat intolerance and increased appetite. She has lost weight: T: 99 F, BP 130/75
mm Hg. On examination, the thyroid gland is mildly enlarged, mobile, and nontender. CN exam nl, mild
lid lag. Laboratory results are as follows:
Free T4 Total T3 TSH
INCREASED INCREASED DECREASED

Radioactive iodine uptake is <5% (normal 8%-25%). The thyroid gland is not visualized on
thyroid scan.]
Which of the following is the MOST LIKELY DIAGNOSIS for this patient?
= PAINLESS THYROIDITIS

[Acute Thyrotoxicosis w/mild thyroid gland enlargement and suppressed TSH. An Autoimmune
disorder – variant of Hashimoto (Hashimoto more chronic hypothyroid)

Educational objective:
 PAINLESS Thyroiditis (silent thyroiditis) = Mild/Brief Hyperthyroid phase with mild thyroid
enlargement and suppressed TSH. Thyroid scintigraphy shows decreased radioiodine
uptake (LOW)….
 Starts HYPERTHROID brief….then pt recovers to nl thyroid function

 Case: Hyperthyroidism (↑TH) & TSH DECREASED

INITIAL NEXT STEP:
Thyroid Radioiodine SCINTIGRAPHY (distinguishes Painless Thyroiditis vs Graves)
o PAINLESS thyroiditis (LOW uptake suggests release of Preformed TH)
o Graves cause hyperthyroid dt increased synthesis of thyroid hormone = DIFFUSE
UPTAKE

SUBACUTE GRANULOMATOUS THYROIDITIS (DE QUERVAIN)

= Painful goiter

RIEDEL THYROIDITIS

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HYPERTHYROID
GRAVES DISEASE – Case: [35yoF palpitations, wt loss, increased appetite, diarrhea in last 2 months. PE:
exophthalmos, lid lag, lid retraction, enlarged & nontender thyroid gland. Low TSH, increased free T4
and T3. Pt diagnosed with Graves’ disease. Various treatment options discussed, she opts for long-term
treatment with METHIMAZOLE.]
Which of following conditions is pt at RISK FOR DEVELOPING FROM THE MEDICATION?
= Agranulocytosis

The 3 major treatment options for Graves' disease are:

1. Radioactive iodine ablation (preferred in the United States) = permanently treats hyperthyroid
2. Antithyroid drugs (ATD): PTU Propylthiouracil & Mthimazole [PTU NOT preferred – Liver
injury/failure]
 PTU for 1st trimester Pregnancy dt Fetal Teratogenicity with Methimazole
 SE: AGRANULOCYTOSIS [inform pt about it]
3. Thyroidectomy (surgery = permanently treats hyperthyroid)

ED:
 Graves' disease can be treated with anti-thyroid drugs, radioactive iodine therapy, or
thyroidectomy.
 Most serious side effect of anti-thyroid drugs is AGRANULOCYTOSIS (0 3% of pts).
o Patients developing SORE THROAT and fever should stop the drug and see a
physician to check their white count WBC

Why WRONG:
Permanent PTU & Methimazole do Radioactive Iodine
Hypothyroidism: not cause renal damage therapy → can worsen
*Results after or risk to kidneys Ophthalmopathy in
radioiodine tx or Graves pts.
thyroidectomy….→
HYPOTHYROID

THYROID STORM

TOXIC MULTINODULAR GOITER

THYROID ADENOMA “Toxic Adenoma”

[31yoF Palpitations & weight loss. BP 140/90 ; Pulse 102/min. Thyroid examination reveals a 2 x 2 cm
left-sided thyroid nodule. Her T3 and T4 are elevated, and TSH is undetectable. Radioactive iodine
scan shows uptake only in the left thyroid nodule. Uptake in the rest of the thyroid is markedly
reduced. Which of the following is the most likely diagnosis?
= Toxic Adenoma:

Why: Clinical features + Labs: increased thyroid hormone levels w/suppressed TSH levels) are
indicative of thyrotoxicosis Furthermore, the radioactive iodine scan shows uptake only in the
left lobe, thereby confirming the diagnosis of toxic adenoma.

Educational Objective:
 Toxic adenoma: Sx suggestive of thyroid toxicosis.
 There is radioactive iodine uptake IN THE NODULE, and suppression of uptake in the rest of
the thyroid gland. Patients with toxic nodule do not have infiltrative ophthalmopathy.

THYROID CANCER

PAPILLARY CARCINOMA

FOLLICULAR CARCINOMA
FOLLICULAR THYROID CARCINOMA FTC – CASE
[58-yo Thyroid Nodule enlarged. There is no associated anxiety, heat or cold intolerance, or recent
change in appetite or weight. No h/o exposure to radiation. Neck examination shows a hard, fixed,
nontender nodule in the right thyroid lobe. Serum TSH level is normaL Ultrasonography of the thyroid
gland shows a 4-cm right lobe nodule. Fine-needle aspiration biopsy shows a large number of
FOLLICULAR CELLS dispersed in clusters and microfollicles]
Which of the following ADDITIONAL FINDINGS WOULD BE MOST CONSISTENT WITH A DIAGNOSIS OF
FOLLICULAR THYROID CANCER in this patient?
=Invasion of the tumor capsule and/or blood vessels

Educational objective:
 Diagnosis of FOLLICULAR THYROID CANCER (FTC) based on a limited tissue sample is not
possible as the cytologic findings are similar to benign follicular adenomas. However,
examination of a surgically excised nodule will SHOW INVASION OF THE TUMOR CAPSULE
AND/OR BLOOD VESSELs. FTC can metastasize via hematogenous spread to distant
tissues.’
 NO LYMPH NODE involvement

Calcitonin: Papillary Thyroid Cancer:u

Secreted by Parafollicular cells of *spread to regional lymph nodes
thyroid *ground glass cytoplasm
*Calcitonin used to diagnosis & *pale nuclei w/inclusion bodies
follow up of Medullary Thyroid *Calcification (Psammoma
Cancer as well as MEN-2 bodies)

MEDULLARY CARCINOMA

ANAPLASTIC CARCINOMA

LYMPHOMA

PITUITARY ADENOMA
TSH-Secreting PITUITARY ADENOMA –CASE
[36yoF frequent headaches and amenorrhea for last 2 months. Weight loss, intermittent Palpitations ,
and vague visual disturbances. Symmetrically enlarged, nontender thyroid gland. Tachycardia with
regular heart rhythm. A fine hand tremor is noted. Labs: Serum T3 222; T4: 13.9; TSH 6.]
Which is Most LIKELY DIAGNOSIS for this patient?
= TSH-secreting pituitary adenoma

Educational objective:
 Case: Central Hyperthyroidism clues: (Elevated Both TSH & TH) + Mass effect (HA, Vision
sx, Impaired pituitary hormone production…amenorrhea)…. TSH-producing Pituitary
Adenoma → likely cause pt’s HYPERTHYROID State

 TSH-secreting pituitary adenomas cause hyperthyroidism with elevated TH & elevated or

inappropriately normal TSH levels. Most TSH-secreting tumors are macroadenomas and
can be associated with mass effect symptoms including headache, visual field defects, and
impaired function of surrounding pituitary tissue.

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HYOPARATHYROIDISM

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HYPERPARATHYROIDISM
PRIMARY HYPERPARATHYROID – CASE:
[Pt has chronic kidney disease dt SLE & NSAID use. Recurrent kidney stones. Calcium 10.8, Albumin 3.9,
Creatinine 1.6, Phosphorus 3.0, Parathyroid hormone 100 (nl: 15-65). DXA bone scan shows T-score -
.25 at lumbar spine, consistent with osteoporosis.]
Which of the following is most LIKELY CAUSE OF PATIENT’S HYPERCALCEMIA?
= Primary Hyperparathyroid

Why:
 Hypercalcemia w/elevated PTH = Primary HPT (Normally elevated Calcium Suppresses PTH
secretion)
 Primary HPT, PTH secreted from Parathyroid adenoma or Parathyroid Hyperplasia is NOT
SUPPRESSED

PTH-independent Hypercalcemia (suppressed PTH-dependent Hypercalcemia: [elevated or

PTH)…dt: inappropriately nl PTH] usually dt:
Cancer, Vitamin D toxicity, Sarcoidosis [extrarenal Primary Hyperparathyroidism
conversion 25 hydroxyvitamin D to 1,25-
Dihydroxyvitamin D]

Educational objective:
 Primary hyperparathyroidism is characterized by PTH SECRETION from parathyroid
ADENOMA or parathyroid HYPERPLASIA
o Most patients have mild, asymptomatic hypercalcemia, but potential clinical
features include nephrolithiasis, osteoporosis, nausea, constipation, and
neuropsychiatric symptoms.

HYPERCALCEMIA OF MALIGNANCY - CASE

[Labs: Calcium 14.8, Parathyroid hormone, intact: 5 (nl: 10-65), Creatinine 1.9, Urea Nitrogen 54mg.
Glucose 180, 25-hydroxyvitamin D: 50 (nl: 20-60), 1,25-Dihydroxyvitamin D 17 (nl: 15-65)
Which is most LIKELY CAUSE OF PATIENT’S HYPERCALCEMIA?
= Hypercalcemia of Malignancy

Educational objective:
 Humoral hypercalcemia of malignancy is the most common cause of parathyroid hormone
(PTH)-independent hypercalcemia and frequently presents with very high, symptomatic
calcium levels. It is due to secretion of PTH-related protein by malignant cells. Other
mechanisms of tumor-related hypercalcemia include osteolytic bone metastasis, increased
production of 1 ,25-dihydroxyvitamin 0 , and increased interleukin-6 levels.
PTH-independent Hypercalcemia (suppressed
PTH)…dt:
Cancer, Vitamin D toxicity, Sarcoidosis [extrarenal
conversion 25 hydroxyvitamin D to 1,25-
Dihydroxyvitamin D]
PTH-dependent Hypercalcemia: [elevated or
inappropriately nl PTH] usually dt:
Primary Hyperparathyroidism (increased PTH)

= LOW/Suppressed PTH

Smoker+fatigue, poor appetite. HIGH Ca, Low PTH

= Cancer → Hypercalcemia (is MCCO PTH-
Independent hypercalcemia)… has >14mg, +
Polyuria, constipation, nausea dt calcium levels

PTHrP (PTH-related protein) = Squamous cell CA

*increase Bone resorption & increase reabsorption
Ca at DCT.
*PTHrP does NOT convert 25-Hydroxyvitamin D to
1,25-Dihydroxyvitamin D like PTH does. = 1,25-
Dihydroxyvitamin D LOW
HYPOCALCEMIA – CASE:
[46yoM bilateral ankle and facial swelling (especially prominent in the periorbital area). His
temperature is 99 F, blood pressure is 130/70 mm Hg, pulse is 78/min, and respirations are 14/min.
Examination shows bilateral 1+ pitting ankle edema. Dipstick urinalysis is positive for protein. A 24-
hour urine collection shows proteinuria of 4.6 g/day: Total serum calcium 7.5mg; Albumin 2.2g,
Phosphorus 3.5mg; Magnesium 2.2mg, Creatinine 0.8mg]
Which of the following is the MOST LIKELY CAUSE OF THIS PATIENT'S LOW SERUM CALCIUM LEVEL?
= Decreased Serum Albumin

Educational objective:
 Patients WITH HYPOALBUMINEMIA CAN HAVE DECREASED TOTAL SERUM CALCIUM.
However, ionized calcium (physiologically active form) is hormonally regulated and remains
stable.

 Calcium binds to albumin…. Hypocalcemia detected in CMP. Got correct the albumin:
0.8mg/dL for ever 1g/dL decrease in serum albumin
Corrected Calcium = (measured total calcium) + 0.8 (4.0g/dL – serum albumin in g/dL)

OSTEOMALACIA-Vitamin D – Case: [Generalized bone pain 4 months after undergoing small-bowel

resection.
His pain is more severe at the lower spine, pelvis, and lower extremities; examination shows tenderness
at these sites. Proximal muscle weakness is noted. X-rays of the lumbar spine show decreased bone
density with blurring of the spine X-rays of the femoral neck show pseudofractures bilaterally]
Which of the following laboratory abnormalities is consistent with this patient's diagnosis?
=
Serum Calcium: Serum Phosphate: Serum Parathyroid Hormone:
LOW LOW INCREASED

ED:
 Osteomalacia due to vitamin D deficiency have low or low-normal serum calcium, low
serum phosphate, increased serum parathyroid hormone, low plasma 25-0H vitamin D
levels, and elevated alkaline phosphatase. Unlike in osteoporosis, most patients complain
of bone pain and muscle weakness. X-ray findings include decreased bone density with
thinning of cortex and pseudofractures (Looser zones)
OSTEOMALACIA – CASE:
[45yoF complaining of fatigue, weakness, and diffuse bone pain. She was diagnosed with celiac sprue 5
years ago and admits to being noncompliant with her diet She takes over-the-counter folic acid and iron
supplements. Labs: Hb 12.2; Calcium 9.0; Phos 2.6 nl, PTH 122 (nl: 10-65), Alkaline Phosphatase 234 (nl
36-92)]
Which of the following is DIRECTLY RESPONSIBLE FOR PATIENT’S CONDITION?
= Impaired Osteoid Matrix Mineralization

Educational objective:
 Osteomalacia [is due to defective mineralization of the organic bone matrix. It is most
commonly due TO SEVERE VITAMIN D DEFICIENCY, which leads to DECREASED INTESTINAL
CALCIUM AND PHOSPHORUS ABSORPTION with resultant secondary hyperparathyroidism

 Typical laboratory findings include hypophosphatemia, hypocalcemia, and elevated

alkaline phosphatase
MALABSORPTION → VITAMIN D DEFICIENCY – Case:
[A 34-year-old woman complains of Diarrhea, weight loss, and fatigue over the last year. “Stools very
foul-smelling and floating”. She complains of diffuse bone pain.]
Which of the following ADDITIONAL FINDINGS would be expected in this patient?

Calcium Phosphate Parathyroid Hormone

LOW LOW HIGH

[Malabsorption/Steatorrhea → Vitamin D deficient → Calcium LOW, Phosphate LOW, PTH HIGH]

[Hypocalcemia → Secondary Hyperparathyroidism [= PTH high]

Educational objective:
 Chronic “foul-smelling diarrhea, weight loss, fatigue” = Steatorrhea & malabsorption
 Chronic GI disease (eg, steatorrhea, celiac disease) can cause vitamin D deficiency due to
malabsorption. [Steatorrhea prevents fat emulsification & disrupts chylomicron mediated
absorption of Vit. D in intestine] → Vit. D deficient
 Patients usually develop hypocalcemia, low phosphorus, and elevated parathyroid hormone
 Patients can be asymptomatic or complain of bone pain or tenderness, muscle weakness or
cramps, and gait abnormalities. [Osteomalacia]

OSTEOPOROSIS
MILK-ALKALI SYNDROME in OSTEOPOROSIS – Case:
[65yoF comes due to a 2-week h/o constipation and abdominal pain. In addition, the patient was
diagnosed with osteoporosis 3 months ago; she declined treatment with bisphosphonates and instead
opted to treat only with over -the-counter vitamin and mineral supplements]
Which of the following is the MOST LIKELY CAUSE OF THIS PATIENT'S CURRENT SYMPTOMS?
= Milk alkali syndrome

Educational objective:
 Case has Typical symptoms of HYPERCALCEMIA: [abdominal pain, constipation, polydipsia.
o [In light of initiation of over-the-counter supplements for osteoporosis 3 months
ago, her symptoms are likely due to milk-alkali syndrome (MAS). MAS is caused by
excessive intake of calcium and absorbable alkali (eg, calcium carbonate
preparations used in patients with osteoporosis). The resulting hypercalcemia
causes renal vasoconstriction and decreased glomerular blood flow.
In addition, inhibition of the Na-K-2CI cotransporter (due to activation of calcium-
sensing receptors in the thick ascending loop) and impaired antidiuretic hormone
activity lead to loss of sodium and free water → Results in hypovolemia and
increased reabsorption of bicarbonate (augmented by the increased intake of
alkali)]
 o Milk-alkali syndrome is caused by EXCESSIVE INTAKE OF CALCIUM AND
ABSORBABLE ALKALI. It can be seen in patients taking CALCIUM BICARBONATE for
osteoporosis Clinical findings include symptomatic hypercalcemia, metabolic
alkalosis, and acute kidney injury
o Meds that raise risk of MAS:
 Thiazides, ACE-I/ATII receptor blockers, NSAIDs

Why WRONG:
Diltiazem side effect: Diabetic Ketoacidosis Thiazide-induced hypercalcemia:
*a CCB – causes constipation…. *Can be initial presentation of *see Mild Hypercalcemia dt:
DM1: Polyuria, polydipsia, increased Calcium Reabsorption
weight loss… in DCT.
But new onset DM1 NOT *Symptomatic Calcemia like this
COMMON in elderly cases IS UNLIKELY to be seen in
Thiazide alone
Vitamin A toxicity:
*Yes Hypercalcemia….but MILD
+ dry skin, headache, blurry
vision clues
NELSON SYNDROME
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PITUITARY ADENOMA: PROLACTINOMA
PROLACTINOMA-CASE:
[37yo + galactorrhea and amenorrhea. Has worsening vaginal dryness, but no headaches or visual
Sx. Visual field testing is normal. Prolactin level is 150 ng/ml (154 ng/ml on repeat measurement), and
thyrotropin (TSH) and serum creatinine are normal. MRI of the pituitary gland reveals a 6-mm
hypointense lesion, as shown in the image below, which is consistent with a pituitary adenoma.]
Which of the following is the most appropriate NEXT STEP IN MANAGEMENT of this patient?
= Treat with Carbergoline

Educational objective:
 [Prolactinoma/high prolactin + galactorrhea, amenorrhea+ Mass] = Prolactinoma
 NEXT STEP?: Treat with CARBERGOLINE

 Patients with a macroprolactinoma (>1 em) or a symptomatic prolactinoma should be

treated with dopaminergic agonists (eg, cabergoline, bromocriptine),→ which can lower
prolactin levels and reduce tumor size.

PROLACTINOMA –
[56yoM 7 -month history of headache, loss of libido, erectile dysfunction, and visual disturbances. On
visual field examination, there is a small temporal field defect seen in both eyes Genitourinary
examination shows atrophic testes. An MRI scan reveals a 1.5-cm pituitary tumor.]
Which of the following BIOCHEMICAL FINDINGS WILL BE MOST CONSISTENT WITH THE DIAGNOSIS OF
A PROLACTINOMA in this patient?
PROLACTIN (nl <15) LH TSH:

200 LOW NORMAL

[>200 PROLACTIN → Cause HYPOGONADISM w/LOW Testosterone levels & LOW or – normal LH

Educational objective:
 Prolactin-producing lactotroph adenoma (prolactinoma) is the most common primary
pituitary tumor. Serum prolactin levels correlate with the size of prolactinoma, and levels
>200 ng/ml are essentially diagnostic.

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ACROMEGALY

ACROMEGALY –Case [“hands getting thick and swollen” “difficulty wearing shoes” BP 150/90. “coarse
facial features, prominent frontal bones and jaws”]
What’s the most common CAUSE OF DEATH in patients with this condition?
= Congestive cardiac failure

ED:
  MCCOD in acromegaly = HEART 38-62%deaths [Coronary heart disease, cardiomyopathy,
arrhythmias, LV hypertrophy, diastolic dysfunction) [HTN occurs in 30%pts, but itself is NOT
solely responsible for increase in CVS mortality]

The following are some non-cardiac causes of death in patients with acromegaly
1. Strokes the incidence of strokes is higher in patients with acromegaly
2. Colon cancer this condition is thought to occur with increased frequency
3. Renal failure this can result from hypertension and hyperglycemia
4. Adrenal failure this can occur due to hypothalamo-pituitary problems due to a pituitary
tumor, although surgical resection and radiotherapy of the pituitary tumor can also cause
secondary adrenal failure

ACROMEGALY - Case
[49yoM Diffuse joint pain, finger swelling, and difficulty gripping objects with his right hand. The
patient has poorly controlled hypertension despite being compliant with medications, a low-salt diet,
and regular exercise. Blood pressure is 146/98 mm Hg. Facial features appear coarse and differ
significantly from his driver's license photograph taken 3 years ago. The palms are sweaty and have a
doughy feel. Tapping the ventral aspect of the right wrist produces shooting pain on the lateral side of
the right hand. Which of the following is the BEST NEXT STEP IN EVALUATING this patient?
= Insulin-like Growth Factor 1 level

Educational objective:
 [Coarse facial features, arthralgias, uncontrolled hypertension, enlargement of fingers,
carpel tunnel sd) = Acromegaly (excessive GH secretion dt Somatotroph ADENOMA)
 GH stimulates HEPATIC Insulin-like growth factor 1 (IGF-1) release → See presentation of
Acromegaly.

 INITIAL NEXT BEST STEP?:

o Measure Insulin-like Growth Factor [is Preferred initial test in suspected
acromegaly]
 (GH is not as sensitive due to wide fluctuations in circulating levels.)

 CONFIRM Test (after finding out have Elevated IGF-1): Glucose Suppression Test
o (nl people: give glucose → suppress GH release)
o (Acromegaly: give glucose → GH NOT suppressed…still released)

 AFTER CONFIRMED by Glucose Suppression Test: NEXT STEP?: MRI brain (check for
mass/last step)

1st: IGF-1 (INITIAL)

2nd: Glucose Suppression Test (confirms)
3rd: MRI brain (last step)
LARON SYNDROME

HYPOPITUITARY
HYPOPITUITARY – CASE:
[36yoM has 6months of fatigue, mild HA, decreased Libido. PE: Decreased testicular volume but is
otherwise normal. Laboratory results are as follows: LH: 0.5; TESTOSTERONE: 100 (NL 240-950), TSH:
(0.05); FREE T4 0.45 (nl: 0.9-1.7); Prolactin 35
Which of the following is the MOST LIKELY DIAGNOSIS?
= Pituitary Adenoma
 Educational objective:
 He has Hypopituitarism featuring: CENTRAL HYPOGONADISM (LOW LH & TESTOSTERONE)
and CENTRAL HYPOTHYROIDISM (LOW TSH & Thyroxine) and mildly elevated Prolactin =
NONFUNCTIONING Pituitary Adenoma → mass (HA, Vision defects, disrupts surrounding
pituitary function)

 Hypopituitarism with a mild to moderate increase in prolactin suggests a nonfunctioning

(gonadotroph) adenoma. Patients may develop symptomatic hypogonadism or
hypothyroidism but are frequently asymptomatic until the adenoma becomes very large
and begins to cause a mass effect on surrounding tissues.

Why WRONG:
Chromosome Hashimoto Thyroiditis
Abnormality: “Chronic autoimmune
*Kleinfelter, has intact thyroiditis”
hypothalamic pituitary = destruction of thyroid
axis….. LH is increased. follicles by immune.

*see LOW free T4 and

ELEVATED TSH
////////////////////////////////////////////////////////////////////////////////////////////////////////
DIABETES INSIPIDUS
PRIMARY POLYDIPSIA – CASE
[Pt has Polyuria + Dilute urine + Increased drinking more water]
*increased urinary frequency. He wakes up several times at night to urinate. His mouth feels dry all the
time and he drinks fluids almost every hour to alleviate his thirst. His sister was diagnosed with diabetes
mellitus at a young age. Laboratory results are as follows: Blood Glucose: 93; Sodium 150; Bicarb 24,
BUN 21, Creatinine 1.1, Uric Acid: 10.1, Osmolality: 314, Urine Osmolality 124.
Which of the following is MOST CONSISTENT WITH THIS PATIENT’S FINDINGS?
= Primary Polydipsia

Polyuria w/DILUTE urine & Primary Polydipsia = DRINK A DI can be Central Or

drinking more water
Polyuria in NON-hospital patient
= usually:
1. DM
2. Primary Polydipsia (aka
Psychogenic Polydipsia)
3. Central or Nephrogenic
Diabetes Insipidus
This Patient’s NORMAL Glucose
makes DM less likely
LOT OF WATER → DILUTES Urine
Nephrogenic
CENTRAL: dt Decreased ADH
release from Pituitary
NEPHROGENIC DI: has Normal
ADH levels w/varying degrees of
RENAL ADH resistance
BOTH types → Decreases Renal
water reabsorption & water loss
w/polyuria → DILUTE URINE &
HYPERNATREMIA

Educational objective:
 Polyuria in nonhospitalized patients can be due to primary polydipsia or diabetes insipidus
(DI)
o Primary polydipsia is due to increased water intake that leads to a dilute urine
(urine osmolality < 1/2 plasma osmolality) and hyponatremia (sodium <137 mEq/L)
Serum Na >145 mEq/L with dilute urine excludes primary polydipsia and favors 0 1.
DI can be central (decreased antidiuretic hormone [AOH] release from pituitary) or
nephrogenic (normal AOH level but with renal AOH resistance)
SYNDROME OF INAPPROPRIATE ANTIDIURETIC HORMONE

//////////////////////////////////////////////////////////////////////////////////////////////////////////////
DIABETES MELLITUS

DIABETIC NEPHROPATHY – Case: [ 60yoM, has EDEMA of face and ankles for 2 weeks. LONG h/o DM,
is managed with exercise, dietary modification, and glyburide. Glycosylated hemoglobin level a month
ago was 6.9%. BP 146/87 mm Hg, pulse is 75/min, and respirations are 15/min. Bilateral pitting edema
around the ankles and periorbital edema.
Laboratory results are as follows: BUN 37mg, Creatinine 2.4mg. Urine protein show 3700mg/24hr.]
What is most appropriate NEXT STEP MANAGEMENT to alter the course of this patient’s diabetic
nephropathy?
= Intensive Blood Pressure control
 ED:
 [INITIAL STEP:] Strict/intensive Blood Pressure Control → most beneficial therapy to reduce
the progression of diabetic nephropathy. Target BP: 130/80mmHg
o [Primary intervention to SLOW decline of GFR]
o Diabetes Mellitus pt: goal : BP 140/90
o Diabetes Nephropathy pt: [has kidney issues] goal: BP 130/80
 ACE-I & ARBs = preferred anti-HTN meds for DM patients. … can reduce intraglomerular
pressure…renoprotective. [CAUTION when use in Diabetic Nephropathy-bc can induce
Acute decline in GFR & Hyperkalemia]

 [Diabetic Nephropathy: Hyperfiltration (increased GFR & Microalbuminuria)…if not treated,

microalbumin can progress to macroproteinuria Urine protein >300mg/24hs, then decline
GFR]

Why WRONG:
Intensive glycemic control:
(HbA1c <7.0%....reduces
progression o
microalbuminuria….BUT, more
aggressive reduction of
glycemic control beyond this
target is related to MORE RISK
FOR HYPOGLYCEMIA & heart
problems

COMPLICATIONS IN DIABETES MELLITUS – Case:

[56yoM DM2 for 15yrs. Current hemoglobin A1c level is 7.5%. Switching to insulin therapy
to attain better glycemic control is discussed with the patient. Intensive glycemic control with a
goal hemoglobin A 1 c of <6.5% is most likely to REDUCE THE RISK OF WHICH OF THE FOLLOWING
COMPLICATIONS?
= Retinopathy

Educational objective:
  TIGHT BLOOD GLUCOSE CONTROL: in patients with DM:
o → DECREASES/REDUCES RISK of microvascular complications (eg, RETINOPATHY,
NEPHROPATHY),

 → INCREASES the risk of HYPOGLYCEMIA (SO NOT CORRECT answer to this Q)

 has an uncertain effect on macrovascular complications (eg, myocardial infarction, stroke =

SO NOT Correct answer to question) and all-cause mortality (so NOT CORRECT answer to Q)

MALIGNANT OTITIS EXTERNA in DM – Case

[72yo intense pain in his right ear, along with ear discharge. The pain is so severe that he is unable to
sleep. “He takes metformin” and enalapril. On physical examination, granulation tissue is noted in the
lower part of his external auditory canal. Cranial nerves are intact. Oropharynx is clear without
exudate.]
Which of the following is the most likely causative organism of this patient's ear condition?
= Pseudomonas Aeruginosa

Educational Objective:
 Suspect malignant otitis externa in any diabetic patient with severe ear pain, otorrhea, and
evidence of granulation tissue in the ear canal.
 Pseudomonas aeruginosa is the most frequent cause of malignant otitis externa.

DIABETES + HYPERLIPIDEMIA – CASE:

[46yoM. No current complaints. h/o DM 2 treated with diet, exercise, and metformin. The patient also
takes a daily aspirin He SMOKES a half pack of cigarettes a day and drinks 1 or 2 glasses of wine 3
times a week. Labs: Total Cholesterol 160mg; HDL 50mg; LDL: 70mg; TG 250mg; HbA1C 6.5%.
Chemistries are in nl limits.]
Which is the most appropriate NEXT STEP IN MANAGEMENT OF THIS PATIENT?
= Add Rosuvastatin

Educational objective:
 DIABETIC patients age 40-75 SHOULD RECEIVE STATIN therapy regardless of baseline lipid
levels. Dose intensity can be selected based on overall risk of cardiac events.

 RF for CAD: DM & Smoking…. DM is controlled, but DM has risk for HEART PROBLEMS
→ so….. STATINS for ALL DIABETICS STATINS lower LDL & Reduce CHD risk
TYPE 1 DIABETES NEW ONSET – CASE
[20yoF lethargy. According to her mother, the patient had a "stomach bug" 4 days ago with nausea,
vomiting, and abdominal pain that began after eating in a local restaurant. Since that time, patient has
had worsening symptoms and decreased oral intake. In addition, over the last few weeks the patient
has experienced a 4-kg (9-lb) weight loss associated with excessive thirst Mucous membranes are dry.
Other than tachycardia, cardiopulmonary examination is normal.]
Which of the following is the most appropriate IMMEDIATE NEXT STEP IN MANAGEMENT of this
patient's illness?
= Fingerstick Glucose

Educational objective:
 Young, Polydipsia, Weight loss = DM type 1
o [DM with Sig Hyperglycemia >180mg → Polyuria…renal Na/Gluc saturated]
 o Deficient Insulin → buildup Ketoacids
o Any GI illness can TRIGGER worsening Hyperglycemia (case above)
o Worsening Hypoglycemia & Metabolic Acidosis: see sx: Abdominal Pain, Altered
mental status, Hyperventilation
 Typical symptoms include weight loss, abdominal pain, hyperventilation, and altered
mentation.
 Diabetic ketoacidosis can be the initial manifestation of type 1 diabetes.
 Presumptive DIAGNOSIS OF DKA: Clinical presentation &
o Check: CAPILLARY BLOOD GLUCOSE can provide rapid presumptive diagnosis.

 INITIAL Treatment NEXT STEP: Immediate Intravenous HYDRATION and INSULIN

 While waiting results, CONFIRMATORY TESTS:

o (VENOUS GLUCOSE, URINE OR PLASMA KETONES, ARTERIAL BLOOD GAS
ANALYSIS)

DIABETIC KETOACIDOSIS DKA –Case:

[21-yoM TDM1 complains of abdominal pain, nausea and vomiting. Chemistry panel shows:
Sodium: 130, Potassium 5.2, Chloride 90, Bicarb 10, Blood glucose 450]
Which of the following is the most appropriate NEXT STEP MANAGEMENT?
= NORMAL saline and REGULAR insulin

Why WRONG:
.45% saline and regular “Normal saline and NPH “Sodium Bicarbonate”
insulin insulin”
= not for INITIAL IV fluid = NPH not for INITIAL; = Not required bc has
bc of its delayed onset side effects
But can change to D5 in & prolonged action = *Cerebral edema…esp
.45 with potassium SLOW children
once Glucose reaches: *shifts Oxy curve
200-250mg left….decreases oxy to
tissues
*can lead to
HYPOKalemia &
Alkalosis

Reserve Sodium-Bicarb
for DKA+Severe
Acidosis <7.1, Bicarb <5,
severe Hyperkalemia

Educational Objective:
The management of DKA involves the following
1. restoration of intravascular volume with normal saline & REGULAR insulin
2. correction of hyperglycemia, electrolyte imbalances, and acidosis
3. treatment of the precipitating cause. The most appropriate initial management is rapid IV
administration of normal saline and regular insulin.

IMPORTANT when manage DKA:

1. Restore Volume: 0.9% saline (nl saline)
2. Correct the hyperglycemia: IV REGULAR INSULIN
3. Correct the electrolyte abnormalities: Potassium correction crucial
4. Treat precipitating factors like infection: Antibiotics

Why: He’s got elevated anion gap (130- [90+10] and acidosis (low bicarb))
To make diagnosis of DKA, need 3 things:
1. Blood Gluc >250mg
2. pH <7.3 or Low serum Bicarb <15-20
3. plasma Ketones detected

HYPEROSMOLAR-HYPERGLYCERMIA NONKETOTIC SYNDROME

HYPEROSMOLAR-HYPERGLYCEMIC STATE -Case
[75yoM w/DM2 has weakness and blurred vision. Over the last several days, he has had a hacking
cough, a sore throat, and poor appetite. His temperature is 100.5F.
There is mild generalized weakness on neurologic examination. Labs shown: K: 5.9, Cl- 101; Bicarb 22;
BUN 52; Creatinine 1.5; Calcium 9.1; Glucose 1070mg.]
Which of the following is most LIKELY PRESENT in this patient?]
= Total Body Potassium Depletion

Educational objective:
 Presentation is HHS: Hyperosmolar-Hyperglycemic State…..likely precipitated by Recent
URT infection.
 HHS & DKA are 2 most serious COMPLICATIONS OF DIABETES!
 DKA: Triad: Hyperglycemia, Ketonemia, Anion Gap Metabolic Acidosis

 HHS: SEVERE Hyperglycemia (>1000), Increased Serum Osmolality >320mOsm.; NO

ketones or acidosis!!

 Despite normal or elevated serum potassium levels [dt: INSULIN deficient &
Hyperosmolality → Promotes Potassium movement OUT of CELLS into ECF]
o patients with hyperosmolar hyperglycemic state (HHS) or diabetic ketoacidosis have
a TOTAL BODY POTASSIUM DEFICIT due to excessive URINARY LOSS caused by
glucosuria-induced OSMOTIC DIURESIS.
o Aggressive insulin therapy for HHS can lower serum potassium levels further and
cause severe hypokalemia LOW potassium = BAD
HHS have NORMAL pH or Slight
Acidemia
*Calcium unchanged
Pt w/severe Hyperglycemia (dt:
HHS or DKA) have total
phosphate depletion due to
Phosphaturia caused by Osmotic
Diuresis
…..NO Renal Phosphate
retention!
GLUCAGONOMA

INULINOMA

SOMATOSTATINOMA

CARCINOID SYNDROME

ZOLLINGER-ELLISON SYNDROME

/////////////////////////////////////////////////////////////////////////////////////////////////////////////
MEN: MULTIPLE ENDOCRINE NEOPLASIA
MEN2B – CASE
[24yoM several enlarging “thyroid nodules”. He’s “Tall with decreased upper-to-lower body ratio”.
Nodules consistent with Neuromas noted on lips and tongue. Hypermobile joints, Kyphoscoliosis.
Normal creatinine and calcium levels, ELEVATED Calcitonin. Biopsy of Thyroid Nodules consistent with
Medullary Thyroid Cancer.]
Which of the following is most LIKELY DIAGNOSIS for this patient?
= Multiple Endocrine Neoplasia
[Marfanoid habitus, mucosal neuromas, Medullary thyroid cancer) = MEN2B…..due GAIN OF FUNCTION
mutation of RET-Proto-oncogene]

Educational objective:
 Type 2B multiple endocrine neoplasia (MEN2B) is characterized by medullary thyroid
cancer, pheochromocytoma, marfanoid habitus, and mucosal neuromas.
 Patients may also have other skeletal deformations (eg, kyphoscoliosis, lordosis).
[In contrast to MEN2A, primary hyperparathyroidism is not seen in MEN2B]

 Medullary Thyroid Cancer (likely due to MEN2B) possible associated Pheochromocytoma

(Asymptomatic….but can have HTN Crisis during Surgery of thyroid mass)….so
NEXT BEST STEP? RET MUTATION test

NEXT IF POSITIVE RET MUTATION TEST: PHEOCHROMOCYTOMA: PLASMA FRACTIONATED

METANEPHRINE ASSAY

MEN: Multiple Endocrine Neoplasia:

[24yoF lump in her neck. Discovered lump 1 week ago while showering. Her mother died during surgery
for thyroid cancer. Blood pressure is 133/80 mm Hg and pulse is 78/min. On examination, there is a
palpable 2-cm nodule in the right thyroid lobe. The remainder of the examination, including chest,
abdomen, extremities, and skin, is normaL Serum TSH and calcium levels are normal and calcitonin is
elevated. Ultrasound-guided aspiration biopsy reveals malignant cells]
Which of the following TESTS IS THE BEST NEXT STEP in evaluation of this patient?
= Plasma Fractionated Metanephrine Assay
 Educational objective:
 Medullary thyroid cancer (MTC) is a CALCITONIN-producing tumor of the thyroid
parafollicular Ccells. It often occurs as a component of multiple endocrine neoplasia types
2A and 2B, which are also associated with PHEOCHROMOCYTOMA (can be
asymptomatic….but when do SURGERY → HYPERTENSION CRISIS!!)

 SCREEN NEXT STEP: screen for Pheochromocytoma PRIOR to Thyroidectomy

o Plasma fractionated METANEPHRINE ASSAY

//////////////////////////////////////////////////////////////////////////////////////////////////////////
Psychogenic Erectile Dysfunction:
[54yoM evaluated for erectile dysfunction. Problems attaining and maintaining erections during sexual
activity for the past 6 months. Prior to the development of this problem, he had an active and
satisfactory sex life. The patient continues to have normal early-morning penile erections. Medical
history is notable for hypertension, mixed hyperlipidemia. His current medications include ibuprofen,
ranitidine, lisinopril, and atorvastatin. Smokes a pack of cigarettes daily and drinks alcohol only on social
occasions. BP 144/78 mm Hg]
Which of the following is the MOST LIKELY CAUSE OF THIS PATIENT'S ERECTILE DYSFUNCTION?
= Psychosocial factors (performance)
Organic causes of ED:
*Hypogonadism
*DM
*Smoking
Sx: INITIAL Intermittent or SLOW
progressive.
Common in Advancing AGE
*NOCTURNAL ERECTIONS – NO
*Early Morning Erections - NO
Vascular or Nerve function to
penis not intact
Psychogenic causes of ED:
*dt interpersonal conflict
*performance anxiety
*emotional stress
= Sudden-onset, situational ED
(eg: ED with certain partner but
nl erection during masturbation)
*KEY: Nonsexual NOCTURNAL
ERECTIONS – YES/ Early
Morning Erections ….means
intact vascular & nerve function
to penis
Beta-Blockers (anti-HTN)
Cause ED
Spironolactone & SSRI =
common causes of ED
Cimetidine (partial anti-
androgenic effects = can cause
ED) [but ranitidine does not
cause ED]
Systemic Atherosclerosis = can
get ED.
*Pt can have RF for
atherosclerotic disease.
*Vascular ED is CHRONIC,
insidious….leads to LOSS OF
NONSEXUAL ERECTIONS