GH

**Synthesis and regulation** - Secreted by somatotrophs (acidophilic cells) of the anterior pituitary. The same family includes prolactin and hPL (human placental lactogen). - Stimulated by GHRH (hypothalamus), ghrelin, sleep (slow-wave), exercise, hypoglycemia, fasting, stress, puberty (sex steroids), L-dopa/clonidine/arginine (used in stimulation tests), and hypothyroidism-independent factors. - Inhibited by somatostatin (SST, from the hypothalamus), IGF-1 (negative feedback at the pituitary and hypothalamus), hyperglycemia/glucose, obesity, and pregnancy-related and aging changes. Somatostatin analogs (octreotide) suppress GH. - Secretion is pulsatile, with the largest pulse during deep sleep. Random GH levels are therefore not diagnostic.

**Mechanism of action** - Receptor: cytokine-type receptor (non-receptor tyrosine kinase) signaling via **JAK2/STAT**. - IGF-1 (somatomedin C) is produced mainly in the liver. It mediates most growth effects through the **IGF-1 receptor (tyrosine kinase)** and is a good screening marker because its level is stable. - Direct (diabetogenic) effects: ↑ lipolysis, ↑ blood glucose (insulin resistance, ↓ glucose uptake), ↑ gluconeogenesis. - IGF-1 effects: ↑ protein synthesis, ↑ chondrocyte proliferation and linear bone growth (epiphyseal plate), ↑ organ growth, ↑ lean body mass. - Other: ↑ muscle mass; GH and IGF-1 also raise phosphate and calcium retention.

**Clinical correlates** 1. *GH excess* - Usually due to a **pituitary somatotroph adenoma** (acidophilic). It can also be ectopic GHRH (e.g., carcinoid, pancreatic tumors). - Before epiphyseal closure → **gigantism**. After closure → **acromegaly**: enlarged hands/feet, coarse facial features, prognathism, frontal bossing, macroglossia, carpal tunnel, hypertrophic cardiomyopathy (leading cause of death), colorectal polyps/cancer, hypertension, insulin resistance/diabetes, sleep apnea. - Diagnosis: ↑ IGF-1, and **failure of GH suppression after an oral glucose tolerance test** (the confirmatory test). Then pituitary MRI. - Treatment: **transsphenoidal surgery** (first line). Medical options: somatostatin analogs (octreotide, lanreotide), pegvisomant (GH receptor antagonist; monitor LFTs, IGF-1 is used to follow response), cabergoline (dopamine agonist). 2. *GH deficiency* - In children: short stature, ↑ fat, delayed bone age, hypoglycemia, midface hypoplasia. Causes include idiopathic, craniopharyngioma, Sheehan syndrome, and Laron syndrome (GH receptor defect: ↑ GH, ↓ IGF-1). Test with a provocative stimulation test (insulin-induced hypoglycemia, arginine, clonidine). Treat with recombinant GH. - In adults: ↓ muscle mass, ↑ central adiposity, dyslipidemia, ↓ bone density. 3. *Pharmacology* - Recombinant GH (somatropin) is used for GH deficiency, Turner syndrome, Prader-Willi syndrome, chronic kidney disease, and idiopathic short stature. Adverse effects: slipped capital femoral epiphysis, intracranial hypertension (pseudotumor cerebri), scoliosis, edema, glucose intolerance. - Misuse as a performance-enhancing drug is a known concern.

**High-yield associations** - Acidophilic anterior pituitary cells: GH and prolactin. Basophils: FSH, LH, ACTH, TSH (B-FLAT). - MEN1 (3 Ps: pituitary, parathyroid, pancreas) can include GH-secreting adenomas. McCune-Albright syndrome can cause GH excess. - GH is a counterregulatory (anti-insulin) hormone, like glucagon, cortisol, and epinephrine. - Also note "GH" can mean other things in other contexts (e.g., gestational hypertension), but in endocrine/physiology contexts it means growth hormone.