Case study 001

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Question 1

Tom is a 43-year-old farmer presented to his family physician with a 3-months history of headache, impaired vision, and occasional nausea and vomiting. He noticed that his shoe size increased, and his fingers got thicker. He also noticed increased thirst and frequency of urination. He has no medical history of chronic illness.

On examination:

Height: 182 cm, Weight: 90 kg, BMI: 27.2
BP: 146/92 mmHg, Heart rate: 72/min, Respiratory rate: 16/min, Temperature: 37.0 0C, O2SAT: 98%
Elongated skull with prominent supra-orbital ridges. Enlarged nose, lips, ear, and prominent jaw. Thickened greasy skin. Crepitus in knee joint.

What do the recent changes in Tom’s physical appearance indicate?

A	Increased effect of the steroid hormones on the body
B	Growth hormone excess in the body
C	Thalassemia major managed by frequent blood transfusion
D	Hypothyroidism

Question 1 Explanation:

Manifestations of growth hormone over-production in adults include enlargement of bones and soft tissue of the head, face, feet, and hands. Since the excessive secretion of growth hormone occurred in adulthood (after closure of epiphyseal plates), Tom's height has not increased significantly. Although thalassemia facies is characterized by some similar facial features such as frontal bossing and maxillary overgrowth, other signs such as big hands and feet are not seen. In adult hypothyroidism, the main facial features are puffiness around the eyes and expressionless face.

Question 2

Tom's laboratory investigation showed:

Blood analysis:
- CBC:
  - RBCs: 4.6 x 10¹²/L, Hemoglobin: 143.5 g/L, Hematocrit: 0.41
  - MCV: 92 fL, MCH: 34 pg, RDW: 11.9%, Reticulocytes: 1.5%, ESR: 10 mm/hour
  - WBC: 9.5 x 10⁹/L, (Neutrophils: 5.7 x 10⁹/L, Lymphocytes: 2.6 x 10⁹/L, Basophils: 0.065 x 10⁹/L, Eosinophils: 0.42 x 10⁹/L, Monocytes: 0.72 x 10⁹/L)
  - Platelet counts: 367 x 10⁹/L
- Na: 137 mmol/L, K: 4.2 mmol/L, Cl: 102 mmol/L, Ca (total): 2.4 mmol/L, Ca (ionized): 1.2 mmol/L
- Glucose: 9.5 mmol/L, HbA1C: 8.3%, BUN: 5.5 mmol/L, Creatinine: 113.3 µmol/L, Uric acid: 332 mmol/L
- Triglycerides: 2.0 mmol/L, Cholesterol: 5.8 mmol/L, HDL: 1.0 mmol/L, LDL: 2.8 mmol/L
- Bilirubin: 6.0 mmol/L, Albumin: 40 g / L
- TSH: 1.5 uU/mL, Total T₄: 85.2 nmol/L, Free T₄: 10.3 pmol/L, Total T₃: 2.3 nmol/L, Free T₃: 5.6 pmol/L
- Plasma Arginine Vasopressin: 3.72 pmol/L
- Aldosterone (recumbent): 0.23 nmol/L
- FSH: 3.4 IU/L, LH: 5.6 IU/L, Prolactin: 3.1 nmol, Testosterone: 18.3 nmol/L, Cortisol: 412 nmol/L
- GH: 389 pmol/L, IGF-1: 65.4 nmol /L
- Osmolarity: 313 mmol/kg
Urinalysis:
- Color: yellow, pH: 5.2, Specific gravity: 1017, Osmolarity : 576 mOsm/kg; Glucose: +, Ketones, Albumin, Bilirubin: negative, WBCs and RBCs: 1 and 0/HPF, Squamous epithelial cells, Bacteria, Casts: negative, Phosphate crystals: ++

If growth hormone (GH) overproduction is suspected, which of the following lab tests should be conducted? (select up to three)

A	CBC
B	Serum GH level
C	Serum GHRH level
D	GH suppression test
E	Plasma osmolarity
F	Serum IGF-1 level
G	GFR and serum creatinine

Question 2 Explanation:

A baseline serum GH level, GH suppression test and the measurement of insulin-like growth factor (IGF-1) are required in the diagnosis of growth hormone excess in the body. IGF-1 is produced primarily by the liver, skeletal muscle in response to GH and stimulates growth of bones, muscles, and other tissue. IGF-1 level is stable throughout the day as opposed to GH, which fluctuates. Please, refer to the methodology section for the explanation of these tests.

Question 3

Growth hormone (GH) suppression test was conducted.

After a 12-hour fasting period, the following are the recordings of plasma glucose and GH levels at baseline and 90 minutes after oral administration of 100g standard glucose solution:

	Baseline	90 minutes
Serum glucose (mmol/L)	9.5	12.9
Serum GH (pmol/L)	389	392

How do you interpret the GH suppression test results?

A	Normal result.
B	Tom’s main health problem is diabetes mellitus since his serum glucose level is high.
C	Physiologically the GH level should decrease after oral glucose intake, so these results support the uninhibited excess production of GH.
D	Physiologically the GH level should significantly increase after oral glucose intake, so these results suggest inadequate GH production.
E	None of the above.

Question 3 Explanation:

GH production should be inhibited by increased blood sugar. If the GH level is not suppressed by the oral glucose intake that supports the over-production of growth hormone.

Question 4

Which of the following statements are correct regarding growth hormone characteristics? (select all that apply):

A	Growth hormone level is normally higher in adults compared to children.
B	Growth hormone is a water-soluble, small peptide hormone that acts on a specific extracellular receptor.
C	Growth hormone is secreted by the posterior lobe of the pituitary gland.
D	Growth hormone and thyroid hormones have synergistic effect on the body.
E	Growth hormone stimulates gluconeogenesis and inhibits the glucose uptake by liver cells.
F	High protein diet and GHRH inhibits GH secretion.

Question 4 Explanation:

GH is secreted by the anterior lobe of the pituitary gland. Hypoglycemia, high protein diet, and GHRH (growth hormone releasing hormone) stimulate the secretion of GH. GH increases the serum glucose level by stimulating gluconeogenesis and inhibiting the cellular glucose uptake.

Question 5

Growth hormone (GH) is also called _________. (fill in the blank)

A	Somatostatin.
B	Somatomedin.
C	Somatotropin.
D	Somatoliberin.
E	Somatocrinin.

Question 5 Explanation:

GH is also called somatotropin. Somatostatin is the other name of growth hormone inhibiting hormone (GHIH), a regulatory hormone secreted by the hypothalamus to inhibit GH secretion. Somatoliberin and somatocrinin are two names of growth hormone stimulating hormone (GHRH), another regulatory hormone secreted by the hypothalamus which stimulate GH secretion. Somatomedins are 3 proteins produced mainly by the liver and have GH-like actions. They include somatomedin A – insulin-like growth factor 2 (IGF-2), somatomedin B – derived from vitronectin, and somatomedin C – insulin-like growth factor 1 (IGF-1).

Question 6

What is the name of Tom’s disorder?

A	Cushing's syndrome
B	Grave's disease
C	Acromegaly
D	Gigantism
E	Marfan syndrome

Question 6 Explanation:

Acromegaly is a condition when the pituitary gland produces excess growth hormone in adults, which results in enlargement of the bony and soft tissue. Acromegaly is a rare endocrine disorder, most commonly caused by pituitary adenoma. Increased growth hormone release in children is called gigantism. Cushing’s syndrome is caused by high level of cortisol production. Grave’s disease is an autoimmune disease of the thyroid gland, resulting in hyperthyroidism. Marfan syndrome is a genetic disorder of the connective tissue which affects the musculoskeletal system, the heart and blood vessels.

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