Endocrinology

Harrison neetss
 Hypopituitarism

• Septo optic dysplasia - Hypothalamic dysfunction and hypopituitarism may

result from dysgenesis of the septum pellucidum or corpus callosum due
mutations in the HESX1 gene - early development of the ventral
prosencephalon.

• Familial and sporadic PROP1 mutation result in combined GH, PRL, TSH, and
gonadotropin deficiency.

• TPIT mutations result in ACTH deficiency associated with hypocortisolism.

• Kallmann syndrome ; hypothalamic hypogonadism, anosmia(olfactory bulb
agenesis), colour blindness, optic atrophy, nerve deafness, cleft palate, renal
abnormalities, cryptorchidism, and neurologic abnormalities such as mirror
movements.
• X-linked KAL gene,
• Autosomal recessive (i.e., GPR54, KISS1)
• Autosomal dominant (i.e., FGFR1)

• Prader willi syndrome : deletion of the paternal copies of the imprinted SNRPN
gene, the NECDIN gene, and possibly other genes on chromosome 15q

• Cranial irradiation: long-term hypothalamic and pituitary dysfunction, especially in

children and adolescents
• (5000 rad) ---- develops over 5–15 years----- hypothalamic damage rather than
pituitary destruction
• GH deficiency is most common, followed by GnRH and ACTH deficiency.
• Lymphocytic Hypophysitis- POSTPARTUM women--- presents with
hyperprolactinemia--- MRI evidence of a prominent pituitary mass that often
resembles an adenoma

Growth hormone

• The growth plate is dependent on a variety of hormonal stimuli, including GH,

insulin-like growth factor (IGF) I, sex steroids, thyroid hormones, paracrine growth
factors, and cytokines.
• Short stature definition: patient’s height is >3 standard deviations (SD) below the
mean for age or if the growth rate has decelerated
• Final height can be predicted using standardized scales (Bayley-Pinneau or Tanner-
Whitehouse) estimated by adding 6.5 cm (boys) or subtracting 6.5 cm (girls) from the
midparental height.
• Peak growth rates occur during midpuberty when bone age is 12 (girls) or 13 (boys).

• Bone age is delayed in patients with all forms of true GH deficiency or GH receptor
defects
• delayed bone age in a child with (short stature)is suggestive of a hormonal or
systemic disorder,
• whereas normal bone age in a (short child) is more likely to be caused by a genetic
cartilage dysplasia or growth plate disorder
• 10% - growth hormone deficiency - GH-N gene mutation

• Recessive mutations of the GHRH receptor - severe proportionate dwarfism-labs:

low basal GH levels that cannot be stimulated by exogenous GHRH, GHRP, or
insulin-induced hypoglycaemia

• Growth hormone insensitivity: defects of GH receptor structure or signalling

• Laron’s syndrome: mutations of the GH receptor
Labs: normal or high GH levels, with decreased circulating GHBP, low IGF1
• defective IGF-I, IGF-I receptor, or IGF-I signaling defects
• STAT5B mutations – associated immunodeficiency
• Growth hormone replacement: 0.02–0.05 mg/kg per day SC

• The sequential order of hormone loss is usually GH → FSH/LH → TSH →

ACTH.
• The most validated test to distinguish pituitary-sufficient patients from those
with AGHD is insulin induced (0.05–0.1 U/kg) hypoglycaemia
• AGHD is defined by a peak GH response to hypoglycaemia of <3 μg/L at
60min
• Also used for growth hormone stimulation : arginine (30 g), GHRH (1 μg/kg),
GHRP-6 (90 μg), and glucagon (1 mg)
• Contraindications to therapy include the presence of an active neoplasm,
intracranial hypertension, an uncontrolled diabetes and retinopathy
• 0.1–0.2 mg/d should be titrated (up to a maximum of 1.25 mg/d) to
maintain IGF-I levels in the mid-normal range for age- and sex-matched
controls
• Total daily dose of hydrocortisone incases of ACTH deficiency should not
exceed 25mg /day.

• Mutations in GPR54, DAX1, kisspeptin, the GnRH receptor, and the LHβ or
FSHβ subunit genes also cause pituitary gonadotropin deficiency.

• Intravenous GnRH (100 μg) stimulates gonadotropes to secrete LH (which

peaks within 30 min)( 3 times rise) and FSH (which plateaus during the
ensuing 60 min).
• The dorsal sellar diaphragm presents the least resistance to soft tissue expansion
from the sella; consequently, pituitary adenomas frequently extend in a suprasellar
direction.
• headache severity correlates poorly with adenoma size or extension.
• visual loss- compression of the optic chiasm
• “stalk section” phenomenon – hyperprolactinemia
• Adenoma on MRI – HYPOINTENSE in T1, HYPERINTENSE in T2
• Incidentalomas: RESECTION - >1cm
• larger masses (>1 cm) are encountered, they should also be distinguished from
nonadenomatous lesions. Meningiomas often are associated with bony
hyperostosis; craniopharyngiomas may be calcified and are usually hypodense,
whereas gliomas are hyperdense on T2-weighted images.

• homonymous hemianopia occurs from postchiasmal compression or monocular

temporal field loss from prechiasmal compression.
• Mc side effect of transsphenoidal surgeries - transient di
• Radiation therapy is usually reserved for postsurgical management.
• Lifelong follow-up with testing of anterior pituitary hormone reserve is
therefore required after radiation treatment.
• Radiotherapy for pituitary tumors has been associated with adverse mortality
rates, mainly from cerebrovascular disease
• Lesions involving the anterior and preoptic hypothalamic regions cause
paradoxical vasoconstriction, tachycardia, and hyperthermia.
• posterior hypothalamic damage causes periodic hypothermia syndrome
• ventromedial hypothalamic nuclei - hyperphagia and obesity
• preoptic nuclei – c DI
• In the absence of radiotherapy, about 75% of craniopharyngiomas recur, and
10-year survival is less than 50%.
• Pituitary metastases occur in ~3% of cancer patients. almost exclusively in
the posterior pituitary. half of pituitary metastases originate from breast
cancer.
• GnRH-producing tumors, children present with precocious puberty,
psychomotor delay, and laughing-associated seizures.
• Pallister-Hall syndrome:mutations in GLI3
• Hypothalamic gliomas and optic gliomas in adults are associated with
neurofibromatosis
• ~15% of all intracranial neoplasms
• About one-third of all adenomas are clinically nonfunctioning and produce no
distinct clinical hypersecretory syndrome. Most arising from gonadotroph cell
which secrete α- and β-glycoprotein hormone subunits
• About 20% of patients (especially males) are resistant to dopaminergic
treatment; these adenomas may exhibit decreased D2 dopamine receptor
numbers or a postreceptor defect.
• Cabergoline also may be effective in patients resistant to bromocriptine.
• improvement of sexual function requires several weeks of treatment but may
occur before complete normalization of prolactin levels.
• Because it is short-acting, bromocriptine is preferred when pregnancy is
desired