DISEASES OF ENDOCRINE

SYSTEM
PITUITARY GLAND
 DISORDERS
• GIGANTISM:
• Excess of GH before fusion of epiphysis.
• ACROMEGALY:
• Excess of GH after fusion of epiphysis.
• CAUSES:
Pituitary adenoma or rarely carcinoma.
MEN 1syndrome
Ectopic ACTH secreting tumor.
• CLINICAL FEATURES:
• Normal height,stout and stocky built.
• Skull - prominent ridges and furrows.
• Visual field defects bitemporal hemianopia
or scotomas.
• Thick lips,macroglossia,thick nose.
• Skin thickening.
• Large frontal and maxillary sinuses.
• Myopathy,arthropathy.
• Large spade like hands thick wide
fingers,large feet.
• Protruding lower jaw – prognathism.
• Hypertension.
• Increase in heel pad >22 mm.
• DIAGNOSIS AND INVESTIGATIONS:
• ↑ levels of GH and IGF 1 may be found in
gigantism but usually normal in
acromegaly.
• In GH secreting tumors ↑ IGF 1 levels and
non supression of GH by glucose to
<1ng/ml.
• MANAGEMENT:
• MEDICAL:
• Dopamine agonists like bromocriptine and
cabergoline lower GH levels.
• Somatostatin analogues like octreotide
lanreotide.
• Pegvisomant GH receptor antagonist.
• SURGICAL:
• Transsphenoidal removal of adenoma with
compressive symptoms.
• Steriotactic ablation by gamma knife
radiotherapy.
• RADIOTHERAPY:
• LINEAR ACCELERATOR
• IMPLANTING YTTRIUM RODS.
• HYPERPROLACTINEMIA:
• CAUSES:
• Cranipharyngioma
• Pituitary tumors like prolactinoma,mixed
pituitary tumors,non functioning tumors.
• DRUG INDUCED:
• DOPAMINE ANAGONISTS:
• Phenothiazines,haloperiol,metoclopramide
.
• DOPAMINE DEPLETERS:
• Reserpine
• Methyl dopa
• OTHERS:
• Oral contraceptives
• PCOS
• Cirrhosis
• Stress ,pregnancy and lactation.
Symptoms and signs:
In males – loss of libido,impotence,visual
field defects,headache
• Prepubertal hypogonadism.
• In females galactorrhea,amenorrhea
infertility ,headache.
• Hypogonadism,delayed onset of puberty.
• INVESTIGATIONS:
• Basal prolactin levels : may be high.
• Visual field defects in large adenomas.
• x ray skull and CT/MRI SCAN.
• Other bio chemical tests like LT, RFT.
• TREATMENT:
• Medical:
• Bromocriptine,cabergoline
• Surgical: pituitary macroadenoma.
• Radiotherapy.
 DWARFISM
1. Physiological
2. Endocrinal:
• Deficiency of GH or GHRH.
• Hypothyroidism
• Panhypopituitarism
• Cushings syndrome
3. Non endocrinal:
• Achondroplasia
• Malabsorption or malnutrition
• Renal diseases
• Familial and chromosomal abnormalities.
INVESTIGATIONS:
STIMULATION TESTS:
• Insulin induced hypoglycemia:
gold standard to confirm or exclude.
• Insulin 0.15 u/kg iv given
• Samples at 0,30,45,60,90 and 120minutes
for blood glucose andGH.
• NORMAL GH>7µg/L
• In Pituitary dwarfism ,patient fails to
respond.
• GH response to GHRH
• Thyroid function tests
• Assessment of bone age.
• TREATMENT:
• Replacement of GH in documented GH
deficient.
 HYPOPITUITARISM
• Hypothalamic causes:
1. Congenital:
• LHRH deficiency- kallmans syndrome
2. Acquired
• Tumors like craniopharyngioma
• Radiation
• Head injury
• TB or sarcoidosis
Histiocytosis.
• PITUITARY CAUSES:
• Tumors
• Radiotherapy
• Head injury
• Haemorrhage
• Autoimmune
• Sheehans syndrome
• SIGNS AND SYMPTOMS:
HORMONE HYPOSECRETION HYPERSECRETION

GH dwarfism – young •Gigantism – young

Cachexia - adult •Acromegaly - adult

ACTH •Atrophy of adrenal •Cushing’s disease

cortex
TSH •Atrophy & depressed •Grave’s disease
thyroid fxn

FSH •Atrophy & infertility •Exaggerated function of

sex organs

•Underdevelopment of •Decreased milk

PROLACTIN
mammary glands production
 MANAGEMENT
• HYPOPITUITARISM
– SURGICAL REMOVAL / IRRADIATION
– REPLACEMENT THERAPY
• THYROID HORMONES
• STEROIDS
• SEX HORMONES
• GONADOTROPINS (restore fertility)
• HYPERPITUITARISM
– SURGICAL REMOVAL / IRRADIATION
– MONITOR FOR HYPERGLYCEMIA &
CARDIOVASCULAR PROBLEMS
 POSTERIOR PITUITARY
DISTURBANCES
• DIABETES INSIPIDUS

• SYNDROME OF INAPPROPRIATE
ANTIDIURETIC HORMONE
 DIABETES INSIPIDUS ABSOLUTE / PARTIAL
DEFICIENCY OF VASOPRESSIN
CRANIAL CAUSES:
CONGENITAL:
• DIDMOAD SYNDROME.
ACQUIRED:
• NEOPLASM OF PITUITARY OR HYPOTHALAMUS
• SURGERY
• HEAD TRAUMA
• VASCULAR
• IDIOPATHIC
• PREGNANCY,PUERPERIUM.
• NEPHROGENIC:
• CONGENITAL
• HYPOKALEMIA
• HYPERKALEMIA
• DIMETHYLCHLORTETRACYCLINE
TOXICITY
• LITHIUM TOXICITY
• HEAVY METAL POISONING
• SIGNS AND SYMPTOMS:
• POLYURIA >3L
• POLYDIPSIA
• Specific gravity OF URINE IS <1.006
• Low URINE OSMOLALITY
• SIGNS OF DEHYDRATION
• SHOCK.
• INVESTIGATIONS:
• 24 URINE VOLUME
• BASAL PLASMA LEVELS OF VASOPRESSIN
• VASOPRESSIN TEST.
MANAGEMENT:
HORMONAL REPLACEMENT – FOR LIFE
VASOPRESSIN – IM OR NASAL SPRAY.
NON-HORMONAL THERAPY:
CHLORPROPRAMIDE – INCREASE
RESPONSE OF THE BODY TO DECREASED
VASOPRESSIN.
SALT RESTRICTED DIET.
MONITOR INPUT AND OUTPUT.
MAINTAIN FLUID & ELECTROLYTE
BALANCE
 THYROID GLAND
• STIMULATED BY THYROID
STIMULATING HORMONE (TSH)
• NEEDS IODINE TO SYNTHESIZE
HORMONE
• SECRETES:
– THYROXINE (T4)
– TRIIODOTHYRONINE (T3)
 HYPERTHYROIDISM
Common causes

Graves' disease Iodide-induced (amiodarone,

contrast)

Multinodular goitre Extrathyroidal source

Factitious thyrotoxicosis
Struma ovarii

Solitary thyroid adenoma TSH-induced

TSH-secreting pituitary adenoma
Choriocarcinoma and hydatidiform mole

Thyroiditis (de Quervain's Follicular carcinoma ± metastases

or Postpartum)
Symptoms SIgns

Weight loss despite normal or increased Weight loss

appetite Tremor

Heat intolerance Palmar erythema

Palpitations Sinus tachycardia

Dyspnoea Lid retraction, lid lag

Irritability, emotional lability

Fatigue, Sweating, Tremor

Less common

Osteoporosis, Diarrhoea, steatorrhoea Goitre with bruit, Atrial fibrillation, HF

Muscle weakness, Pruritus, Ankle swelling Systolic hypertension/increased pulse

Alopecia pressure

Amenorrhoea/oligomenorrhoea Hyper-reflexia, Ill-sustained clonus,

Infertility, spontaneous abortion Proximal myopathy
 Jod-Basedow phenomenon
• is hyperthyroidism following administration
of iodine or iodide, either as a dietary
supplement or as contrast medium.
• This phenomenon is thus iodine-induced
hyperthyroidism, typically presenting in a
patient with endemic goiter (due to iodine
deficiency).
• GRAVES DISEASE
• The most common cause of
hyperthyroidism
• Autoimmune disorder characterized by
IgG antibodies to thyroid-stimulating
hormone receptors on thyroid cells
• Etiology is unknown present in family
members
• Occurs at any age, esp. in 3rd & 4th
decades
– Women > men
– Other autoimmune conditions may be present
in family members
– Physical Signs
• – hyperthyroidism
• – “classic” triad: diffuse goiter, dermopathy,
ophthalmopathy
• Upper lid retraction (Dalrymple sign) -
90%

33
 Restrictive myopathy

Elevation defect Abduction defect

34
Depression defect Adduction defect
Mobius sign (poor convergence)
 Mechanisms for upper lid retraction

Up gaze restriction Proptosis

Fibrotic contracture of LPS

Secondary over action of LPS-SR complex
Muller muscle over action
36
Lid lag on down gaze
(von Graefe’s sign)

37
Glabellar furrows Eyelid edema

38
 Stellwag sign (incomplete and infrequent blinking)
 Goffroy sign (absent creases in the forehead on superior
gaze)
 Enroth’s sign (eyelid fullness)
Gifford’s sign
(difficulty in upper lid eversion

39
Minimal staining
Corneal signs

Ulceration

perforation

40
 Ballet sign
– restriction of one or more extra ocular muscles
– Initially due to edema , later fibrosis
– All 4 recti are involved but mainly IR and MR

41
• Treatment:
– Reducing thyroid hormone synthesis:
• Antithyroid drugs (Methimazole, Propylthyouracil)
• Radioiodine (131I)
• Subtotal thyroidectomy
– Reducing Thyroid hormone effects:
• Propranolol
• Glucocorticoids
• Benzodiazepines
– Reducing peripheral conversion of T4 to T3
• Propylthyouracil
• Glucocorticoids
• Iodide (Large oral or IV dosage) (Wolf-Chaikoff
effect)
• TOXIC NODULAR GOITER
• More common in the elderly than Graves
disease

• • Caused by multiple (most common) or a

single hyper functioning thyroid nodule
• • May develop in long standing simple
goiter; otherwise, etiology is unknown
• Physical signs– enlarged, nodular thyroid–
hyperthyroidism
• – CHF, arrythmias often present because
of age group affected
• – ophthalmopathy, dermopathy usually
absent

• Diagnostic Studies
• – decreased TSH
• – increased free T4/T3
• – RAIU and scintiscan
• – TSH receptor antibodies are absent
Treatment
• – radioactive iodine generally TOC
• – anti thyroid drugs
• – surgery
– Thyrotoxic crisis or Thyroid storm:
• It´s a life-threatening exacervation of thyrotoxicosis,
acompanied by fever, delirium, seizures, coma, vomiting,
diarrhea, jaundice.
• Mortality rate reachs 30% even with treatment

• It´s usually precipitated by acute illness, such as:

Stroke, infection,trauma, diabeic ketoacidosis,
surgery, radioiodine treatment
Treatment:
• Fluids
• Antibiotics
• Beta blockers
• Glucocorticoids
• Iodine therapy(sodium iopodate)
• Anti thyroid drugs.
 Hypothyroidism
• Signs and symptoms:
• Tiredness, fatigue, weakness
• Cold intolerance, hoarseness, dry skin
• Constipation, muscle cramps
• Mental impairment, depression
• Menstrual disturbances, infertility
• Weight gain, median nerve disturbances
• Dyspnea, chest pain, peripheral edema
• Hair loss, facial edema, deafness
• Dry hair, dry skin, hair loss
• Deep voice, large tongue, deafness
• Thyromegaly, bradycardia, edema
Diagnosis:
• Primary hypothyroidism is
characterizedby decreased free T4 and
elevated TSH
• Hypothyroidism secondary to
hypothalamic or pituitary conditions shows
decreased free T4 and normal or
decreased TSH
• “Subclinical” hypothyroidism is
characterized by absence of symptoms,
normal free T4, and elevated TSH
• Antithyroid antibodies are elevated in
autoimmune thyroiditis (Hashimoto’s)
• TREATMENT:
• Levothyroxine
• re-evaluation at 8-week intervals until
stable; thereafter every 6-12 months.
PARATHYROID GLAND
DISORDERS
 PARATHORMONE ACTION
Increase serum calcium Decrease serum
level by: phosphate level by:

Ca re-absorption from Increase serum excretion

renal tubules. of phosphate.
Ca absorption from the
GIT.
Bone resorption
 Hyperparathyroidism

Primary Secondary Tertiary

Parathyroid Parathyroid Parathyroid Autonomous

Parathyroid
nodule on top
hyperplasia adenoma carcinoma hyperplasia of hyperplasia
 Laboratory Diagnosis
– all cases Elevated Serum Ca and PT.
Must measure Ionized Ca (subtle cases
of hyperPTH will have normal Serum
Ca)
• 50% will have hypophosphatemia
Elevated Alkaline Phosphatase in 10-40%
• Hyperchloremic metabolic acidosis
• Low Mg in 5-10%
• High Urinary Ca in many.
 TREATMENT
• Definitive therapy - resection
• Must reverse hypercalcemia by
– Hydration and Diuresis
– bisphosphonates.
Hypocalcemia after surgery is treated by oral
calcium and vitamin D analogues.
 TREATMENT

• ORAL CALCIUM
• VITAMIN D ANALOGUES
ADRENAL GLAND DISORDERS
CUSHINGS SYNDROME
 NELSONS SYNDROME
Occurs after bilateral adrenalectomy without
pituitary fossa irradiation for treatment of
cushings disease.
Hyperaldosteronism
 Causes

• Nephrotic syndrome
• Cirrhosis o liver
• Congestive heart failure
• Malignant hypertension
• Renal artery stenosis
• Barters syndrome.
• SIGNS AND SYMPTOMS:

• Water and sodium retention.

• Potassium excretion in exchange of

hydrogen ions causing symptoms of
hypokalemia and alkalosis like muscle
weakness,polyuria,tetany,ecg
changes,arrythmias.
 Investigations

• Plasma potassium
• Plasma or urinary aldosterone estimation
• Plasma rennin activity
• Others like CT abdomen,adrenal scanning
with selenium for adenoma.
 Treatment
• Drugs
• Spironolactone or epleronone
• Surgery for adenomas.
• Secondary hyperaldosteronism is treated
according to the cause.
• investigations:
– Hypoglycemia
– Hyponatremia
– Hyperkalemia
– Increased WBC (leukocytosis)
• ACTH stimulation test:
– Short test-compares blood cortisol levels before
and after 250 micrograms (IM/IV) given.
– Long test-uses 1 mg . Blood is taken 1, 4, 8, and
24 hours later.

Increased ACTH level: Primary insufficiency

Decreased ACTH level: Secondary
insufficiency
 complications
• Addisonian crisis - characterized by cyanosis
and signs of circularory shock:
• pallor
• rapid and weak pulse
• rapid respirations
• low blood pressure
• severe vomiting and diarrhea
• lethargy
• hypercalcemia
 Treatment

• Replacement therapy:
• Oral prednisolone
• Fludrocortisone
• Treatment o causes like antitubercular
drugs for TB.
 DISEASES OF ADRENAL
MEDULLA
• PHEOCHROMOCYTOMA:
• TUMOR OF CHROMAFFIN TISSUE
SECRETES EPINEPHRINE AND
NOREPINEPHRINE.
 INVESTIGATIONS

24 HOUR urinary
• Vinyl mandelic acid
• Metanephrines
• free catecholamines are elevated
Plasma metanephrines and
normetanephrines are elevated.
• CT OR MRI.