A 42-year-old man who is employed as a construction worker presents to his primary care physician with complaints of moderate headaches and profuse sweating. He reports the need to carry up to 3 additional shirt changes to work because they drench quickly even with tasks of low physical exertion. His coworkers have commented about his changing glove and boot sizes, which have increased at least 4 times since he joined the company 10 years ago. Physical examination is unremarkable except for blood pressure of 160/95 mm Hg, hyperhidrosis, noticeably large pores, hypertrichosis, widely spaced teeth, and prognathism. Which of the following best explains the patient’s clinical manifestations?

Increased serum insulin-like growth factor 1 (IGF-1)

Increased thyroid-stimulating hormone

A 40-year-old woman visits her physician’s office with her husband. Her husband says that she has been complaining of recurring headaches over the past few months. A year ago she was diagnosed with diabetes and is currently on treatment for it. About 6 months ago, she was diagnosed with high blood pressure and is also taking medication for it. Her husband is concerned about the short span during which she has been getting all these symptoms. He also says that she occasionally complains of changes and blurring in her vision. In addition to all these complaints, he has observed changes in her appearance, more prominently her face. Her forehead and chin seem to be protruding more than usual. Suspecting a hormonal imbalance, which of the following initial tests would the physician order to indicate a possible diagnosis?

Serum insulin-like growth factor-1 (IGF-1)

Pituitary magnetic resonance image (MRI)

A 1-year-old male presents to his pediatrician for a well-child visit. Through a history from the mother and physical examination, the pediatrician learns that the baby babbles non-specifically, takes several steps independently, and picks up his cereal using two fingers. His weight is currently 22 lbs (birth-weight 6 lbs, 9 oz), and his height is 30 inches (birth length 18 inches). Are there any aspects of this child's development that are delayed?

There are no developmental concerns

Two hours after a 2280-g male newborn is born at 38 weeks' gestation to a 22-year-old primigravid woman, he has 2 episodes of vomiting and jitteriness. The mother has noticed that the baby is not feeding adequately. She received adequate prenatal care and admits to smoking one pack of cigarettes daily while pregnant. His temperature is 36.3°C (97.3°F), pulse is 171/min and respirations are 60/min. Pulse oximetry on room air shows an oxygen saturation of 92%. Examination shows pale extremities. There is facial plethora. Capillary refill time is 3 seconds. Laboratory studies show: Hematocrit 70% Leukocyte count 7800/mm3 Platelet count 220,000/mm3 Serum Glucose 38 mg/dL Calcium 8.3 mg/dL Which of the following is the most likely cause of these findings?

Transient tachypnea of the newborn

A 5-day-old male newborn is brought to the physician by his mother because of yellowish discoloration of the skin for 1 day. The discoloration first appeared on his face and then spread to his trunk. There have been no changes in his bowel habits or urination. He was born at 38 weeks' gestation via uncomplicated vaginal delivery. He is exclusively breastfed every 2–3 hours. Examination shows scleral icterus and jaundice of the face, chest, and abdomen. Laboratory studies show: Hemoglobin 17.6 g/dL Reticulocytes 0.3% Maternal blood group A, Rh-negative Fetal blood group 0, Rh-positive Serum Bilirubin, total 7 mg/dL Direct 0.6 mg/dL Free T4 12 μg/dL Which of the following is the most likely diagnosis?

Physiological neonatal jaundice

A 1-month-old girl presents to her pediatrician with her mother. The patient was born at 38 weeks gestation via Caesarian section for cervical incompetence. The patient’s mother has no complaints, although she notes that the child had a runny nose and cough for a few days last week. The patient’s mother endorses decreased appetite during the aforementioned illness which has now returned to baseline. The patient’s family history is significant for an older brother with glucose-6-phosphate dehydrogenase (G6PD) deficiency and a maternal uncle with cirrhosis secondary to chronic hepatitis B. On physical exam, the patient has scleral icterus and dark urine staining her diaper. Laboratory testing reveals the following: Serum: Na+: 137 mEq/L Cl-: 102 mEq/L K+: 4.2 mEq/L HCO3-: 24 mEq/L Urea nitrogen: 12 mg/dL Glucose: 96 mg/dL Creatinine: 0.36 mg/dL Alkaline phosphatase: 146 U/L Aspartate aminotransferase (AST): 86 U/L Alanine aminotransferase (ALT): 76 U/L Total bilirubin: 4.6 mg/dL Direct bilirubin: 3.8 mg/dL Which of the following is the most likely diagnosis?

Obstruction of the extrahepatic biliary tree

Increased production of bilirubin

Increased enterohepatic circulation of bilirubin

Decreased metabolism of bilirubin

Obstruction of the intrahepatic biliary tree

Growth hormone disorders — USMLE Lesson

GH Physiology - The Growth Blueprint

Secretion: Pulsatile, with largest peak during deep sleep (Stage N3).
Actions (Dual Role):
- Direct: Anti-insulin effects (↑ lipolysis, ↑ blood glucose).
- Indirect: Via IGF-1 from liver; mediates linear growth (epiphyseal plates) and protein synthesis.

⭐ Screening for GH disorders relies on IGF-1 levels, not random GH, due to GH's pulsatile release versus IGF-1's stable, longer half-life.

Growth Hormone-IGF-1 Axis: Wildtype vs. IGF-1R KO

GH Deficiency - The Short Story

Etiology
- Congenital: Idiopathic (most common), genetic (e.g., GH1, GHRHR mutations), midline defects (septo-optic dysplasia).
- Acquired: Craniopharyngioma (most common tumor), CNS radiation, trauma, infection.
Clinical Features
- Neonate: Hypoglycemia, micropenis, prolonged jaundice.
- Child: Short stature (height < -2 SD), ↓ growth velocity, delayed bone age, cherubic facies, truncal obesity, high-pitched voice.
Diagnosis & Treatment
- Screening: ↓ IGF-1 & IGFBP-3.
- Confirmation: GH stimulation tests (Insulin, Clonidine). Peak GH < 10 ng/mL is diagnostic.
- Imaging: Pituitary MRI to identify structural causes.
- Treatment: Recombinant Human GH (rhGH).

Child with GHD: cherubic facies, truncal obesity, MRI, X-ray

⭐ Laron Syndrome: A GH receptor defect causing GH insensitivity. Presents with features of GHD but has ↑ GH and ↓ IGF-1 levels.

GH Excess - Towering Troubles

Etiology: Most commonly a pituitary adenoma.
Clinical Manifestations:
- Gigantism: Before epiphyseal fusion. Symmetrical overgrowth, ↑ height.
- Acromegaly: After epiphyseal fusion. Coarse facial features, frontal bossing, prognathism, macroglossia, spade-like hands/feet.
- Systemic: Cardiomegaly, hypertension, insulin resistance (diabetes).

Gigantism: Excess GH from macroadenoma causes rapid growth

Diagnosis:

⭐ Most specific test: Oral Glucose Tolerance Test (OGTT). Failure to suppress GH levels below 1 ng/mL after a 75g glucose load is diagnostic.

Management:
- 1st Line: Trans-sphenoidal surgery.
- Medical: Somatostatin analogs (Octreotide), GH receptor antagonists (Pegvisomant).

Laron Syndrome - Unresponsive Receptors

Pathophysiology: Autosomal recessive mutation in the Growth Hormone Receptor (GHR) gene, causing end-organ insensitivity to GH.
Biochemical Profile: ↑ GH, but ↓↓ IGF-1 & IGFBP-3. This paradoxical finding is key.
Clinical Features: Severe short stature, prominent forehead, depressed nasal bridge, small hands/feet, and hypoglycemia.
Treatment: Ineffective GH therapy. Requires Recombinant IGF-1 (Mecasermin).

⭐ Exam Pearl: Despite obesity, patients with Laron syndrome have a significantly lower incidence of cancer and diabetes mellitus.

Normal vs. Laron syndrome GH signaling and growth

High‑Yield Points - ⚡ Biggest Takeaways

GH deficiency is a key cause of pathological short stature, often with neonatal micropenis and hypoglycemia.

Screening involves IGF-1/IGFBP-3 levels; confirmation needs GH stimulation tests (e.g., insulin-induced hypoglycemia).

Laron syndrome (GH insensitivity) is a receptor defect presenting with high GH but low IGF-1.

GH excess causes gigantism before epiphyseal fusion and acromegaly after.

The most common cause of GH excess is a pituitary adenoma.

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