by West Medical Ward King Edward Medical University , Lahore, Pakistan.

1. The Endocrine System

2. Endocrine Disorders
• Disease states that result from excess
or insufficiency of hormone
• Clinical challenge is determination of the
origin of excess or insufficiency, i.e.,
Hypothalamus (tertiary), Pituitary (secondary)
or target gland (primary)

3. Endocrine Disorders
(Other than diabetes)
• Thyroid
• Adrenal
• Parathyroid
• Pituitary gland
• Gonadal
• Gout (uric acid)

4. Hypothalamus
ACTH = adrenocorticotropic hormone
LH = lutenizing hormone
FSH = follicle-stimulating hormone
AVP = arginine vasopressin
CRH = corticotropin-releasing hormone
GHRH = growth hormone-releasing hormone
GnRH = gonadotropin-releasing hormone
GH = growth hormone
TSH = thyroid-stimulating
hormone
PRL = prolactin
SRIF = somatotropin release–inhibiting factor
(somatostatin)
TRH = thyrotropin-releasing hormone;
VIP = vasoactive intestinal polypeptide.
DA = dopamine
Goldman: Cecil Medicine, 23rd ed. 2007

5. Hormone Target Gland
Growth hormone (GH) Multiple
Prolactin (PRL) Breast
Adrenocorticotropic hormone
(ACTH)
Adrenal
Thyroid-stimulating hormone
(TSH)
Thyroid
Luteinizing hormone (LH) Gonad
Follicle-stimulating hormone
(FSH)
Gonad
Anterior Pituitary Hormones

6. Anterior Pituitary Hormones
• TSH, ACTH, FSH, and LH hormones are
tropic hormones that simulate other
endocrine glands
• TSH-Thyroid
• ACTH- Adrenal Cortex
• FSH, LH- Gonads

7. Posterior Pituitary Hormones
• Vasopressin(ADH)- kidney, baroreceptors
(plasma osmolality, water retention, thirst)
• Oxytocin- breast, uterus (no
known function in males)
• Both are synthesized in specialized neurons
in the hypothalamus (neurohypophyseal
neurons)

8. Too big, Too tall
or
Too short
Prof. Tariq Waseem

10. CASE SCENARIO 1
• A 50 yr old male presented in OPD with C/O
off & on headache, poor concentration and
fatigue. He has gained weight, he sweats a
lot. He also has difficulty in churning the food
bolus in mouth and food particles are stuck in
his unusually widened teeth spaces. His skin
has coarsened and has developed multiple
skin tags. His friends report that he has a
heavy, doughy and sweaty handshake and
often does not notice people sitting on either
sides of his desk.

11. • O/E
• BP 160/100.
• Displaced cardiac apex in 6th i.c. space.
• Hepatosplenomegaly.
• BSR 240mg/dl
• Glycosuria ++

13. • What is the diagnosis?
• What is the best test to diagnose this
condition?
• List three further investigations to confirm the
diagnosis.

14. GROWTH HORMONE
•Single chain 191
amino acid anabolic
polypeptide
synthesized by
somatotropic cells of
anterior pituitary gland.
•Fasting serum values
<5ng/ml

15. BIOREGULATION & EFFECTS
GHRH, Ghrelin
Sex hormones
Sleep, fasting,
exercise, arginine
Somatostatin
Hyperglycemia
Glucocorticoid
IGF
RAISED IGF –
Impair insulin
sensitivity.
HYPERGLYCEMIA-
breakdown of
pancreatic islets

16. CAUSES OF
GH-DEFICIENCY GH-EXCESS
• CONGENITAL
ABNORMALITIES
• INTRACRANIAL
TUMORS
(CRANIOPHRANGIOMA)
• IRRADIATION,
SURGERY OR TRAUMA
• SHEEHAN SYNDROME
• AUTOIMMUNE
•MICRO OR
MACROADENOMAS
•IN ASSOCIATION WITH
MEN-I
•RARELY BY ECTOPIC GHRH

17. ACROMEGALY
ACROMEGALY is a condition in adults
caused by hyper secretion of GH hormone
after the closure of epiphyseal plates.
GIGANTISM occurs if growth hormone excess
starts in in children or adolescents before
epiphyseal closure.
GIGANTISM

18. Epidemiology
• Acromegaly is more common than gigantism,
with an incidence of 3-4 cases per million
people per year and a prevalence of 40-70
cases per million population.

19. Genetics
• In gigantism inherited and manifested during
childhood or adolescence GPR101, a gene
on the X chromosome, is overexpressed.
• A mutation in the GPR101 gene was found in
about 4% of cases of Acromegaly.
• The GPR101 gene may be a target for the
treatment of growth disorders.

20. SIGNS & SYMPTOMS

21. SIGNS & SYMPTOMS

22. BEFORE & AFTER…..

23. COMPLICATIONS
 Hypopituitirsm
 Visual defects
 Hypertension
 Glucose intolerance/ frank DM
 Cardiomegaly / cardiac failure
 Carpal tunnel syndrome
 Cord compression
 Colon polyps

24. LABS
 Serum Growth Hormone (Unreliable)
 Raised IGF-I, IGF binding protein IGFBP-3
 Hypercalcemia
 Hyperphosphatemia
 T4 & TSH Low (secondary hypothyroidism)
 Hyperprolactinemia(mammosomatotrophs are the most
common type of GH-secreting cells involved in childhood gigantism
 Hyperglycemia
GLUCOSE TOLERANCE TEST
A 75g glucose syrup is given orally and serum GH
levels are measured @ 60, 90, 120 min.
ACROMEGALY is excluded when levels are < 1ng/ml

26. IMAGING
X-Ray Hands X-Ray Skull Lat. MRI Pituitary

27. Other Tests
ECG
Echocardiography
Colonoscopy

28. TREATMENT
• 1ST Line PITUITARY MICROSURGERY
• 2ND Line RADIOSURGERY
• 2nd Line MEDICAL
Somatostatin analogue
Dopamine agonist
GH receptor antagonists

29. MICROSURGERY
• Trans sphenoidal hypophysectomy has the
dual advantage of rapidly improving
symptoms caused by mass effect of the
tumor and significantly reducing or
normalizing GH/IGF-I concentrations.

30. RADIOTHERAPY
• External radiotherapy is given in cases of
remissions after surgery.
• Gamma Knife Surgery
• Associated with risks of panhypopitutirsm.

31. MEDICAL THERAPIES
As 2nd line therapy after surgery to reduce GH
levels < 5mU/l
DOPAMINE AGONISTS
CABERGOLINE effective in tumors secreting
both prolactin & GH.
SOMATOSTATIN ANALOGUE
OCREOTIDE & lanreotide given as s/c
injections.
GH RECEPTOR ANTAGONISTS
PEGVISOMANT is used primarily for
symptomatic relief.

32. Treatment
• Cure, or adequate control, of growth
hormone (GH) excess is defined as a
glucose-suppressed GH concentration of
less than 2 ng/mL, as determined by
radioimmunoassay (1 mcg/L by IRMA), and
normalization of the serum insulinlike growth
factor I (IGF-I) concentration.

33. Summary
Acromegaly is a rare, insidious, and potentially
life-threatening condition for which there is
good, albeit incomplete, treatment that can add
years of high-quality life for the patient.
Increased and unregulated growth hormone
(GH) production, usually caused by a GH-
secreting pituitary tumor (somatotroph tumor),
characterizes acromegaly.

35. • What is the diagnosis?
• What is the best test to diagnose this
condition?
• List three further investigations to confirm the
diagnosis.

36. Stockholm Sweden

37. CASE SCENARIO 2
• A mother brings her 15 yr old son to the
OPD complaining he has not gained height
compared with his siblings and classmates.
He is depressed and feels socially isolated.
He is 3.5 ft tall with thin skin and wrinkles,
decreased body tone. His mother complains
of his unsocial behavior at home and lack of
interest in studies.
• What can be reasons of his short stature?

38. DIFFERENTIALS
• Familial short stature
• Constitutional delay
• GH deficiency
• Achondroplasia
• Vitamin D deficiency
• Sex hormone deficiency

39. PROPOTIONATE DIS PROPPORTIONATE
TYPES OF DWARFISM

40. SIGNS & SYMPTOMS OF GH-
DEFICIENCY
•Retarded growth
•Central obesity
•Psychogenic symptoms
•Decreased bone and muscle mass
•Thin skin with fine wrinkles
•Poor sweating or temperature regulation
•Decreased energy and endurance
•Low energy levels
•Increased cholesterol and LDL
•Increased systolic blood pressure
•Decreased cardiac output
•Overproduction of insulin

41. Lab tests for GH Deficiency
• LOW IGF-I LEVELS
• INSULIN TOLERANCE TEST
• GHRH + ARGININE STIMULATION TEST
AVOID IN PTS WITH SEIZURES & CAD
AVOID IN PTS WITH KIDNEY &LIVER DISEASE

42. LARON SYNDROME
• Autosomal recessive disorder due to
mutations in the gene for GH receptor.
• Resistance to GH resulting in IGF-I
DEFICIENCY.
• Show resistance to DIABETES.
•Dwarfism
•Depressed nasal bridge
•Underdeveloped mandible
•Central obesity
•Hypoglycemic seizures
BIOSYNTHETIC IGF-I
BEFORE PUBERTY

43. 4
Stockholm Sweden