Endocrine Flashcards
*
clinical features of Diabetes Mellitus
-
“Honeymoon period”: First 1-2 years after
manifestation of overt type 1 diabetes - Hyperglycaemia
- Glycosuria –> Osmotic Diuresis –> Polyuria
- Polydipsia (increased thirst)
- Polyphagia (excessive hunger)
- Ketoacidosis (severe cases) [type 1 DM]
- Hyperosmolar non-ketotic coma (sever dehydration) [type 2 DM]
- Weight loss [type 1 DM]
- Obesity [type 2 DM]
honeymoon : pancreas is still able to produce small amounts of insulin
Histology of Type 1 vs Type 2 diabtes Mellitus
Type 1: “insulitis” ; Islets lymphocytic infiltrates (made up of macrophages and lymphocytes)
Type 2: Islet Amyloid polypeptide (IAPP) deposists
Type 1 vs Type 2 diabetes
Explain the Pathology of how islets are replaced by Amyloid in Type 2 DM
1) inadequate compensation for peripheral resiatnce –> Hyperglycaemia + loss of β-cell mass
2) Excess FFAs and glucose –> lymphocytic infiltration (Recruitment of macrophages and T cells) –> Cytokine production –> Beta cell dysfunction and death
3) Replacement of islets by amyloid
list 4 Diabetic Macrovascular diseases
1) MI
2) Atherosclerosis of the aorta and large/medium-sized arteries
3) Gangrene of the lowere extremities
4) Hylaine Arteriosclerosis [associated with hypertension]
list 3 complications of Diabetic Microangiopathy
1) Diabetic Nephropathy (Glomerulosclerosis, Pyelonephritis, Hylaine Arteriolosclerosis)
2) Retinopathy (cataracts, Galucoma)
3) Neuropathy (nerve injury in the legs and feet)
Diabetic Nephropathy
poorly controlled diabetes can cause damage to blood vessel clusters , leading to Glomerular lesions –> kidney damage. Explain how this happens
Changes in the apperance of the glomerulus due to lesions:
GBM thickening –> Mesangial expansion (Diffuse mesangial sclerosis) –> Nodular glomerulo-sclerosis (Kimmelstiel-Wilson lesions) –> Diffuse glomeurlosclerosis (chronic)–> kidney damage due to Ischaemia
* GBM : Glomerular Basement Membrane
Non-proliferative vs Proliferative Diabetic Retionopathy
Non-proliferative
–> Microangiopathy,retinal haemorrhages and exudates (“soft” = microinfarcts, “hard” = deposits of plasma proteins and lipids), micro-aneurysms and oedema
Proliferative:
–> Process of neovascularisation and fibrosis; Vitreous haemorrhages, due to rupture of newly formed vessels –> Organisation of the haemorrhage –> Retinal detachment
*Vitreous Haemorrhage : presence of blood in the vitreous humor
The 2 PanNETs associated with MEN-1 syndrom (mutation)
*PanNETs: Pancreatic Neuro-Endocrine Tumours
1) Insulinomas (in the pancerase)
2) Zollinger-Ellison Syndrome (Gastrinomas)
primary causes of Thyrotoxicoses associated w/ Hyperthyrodism
1) Diffuse toxic hyperplasia (Grave’s disease)
2) Hyper-functioning (“toxic”) multi-nodular goiter
3) Hyper-functioning (“toxic”) adenoma
4) Iodine-induced hyperthyroidism
diagnostic tests for Hyperthyroidism
- increased T3/T4
- Decreased TSH (if Primary)
Measurement of radioactive iodine uptake by the
thyroid gland
* Diffusely [increased/decreased] uptake in Grave’s disease
* [Increased/decreased]uptake in a solitary nodule in toxic adenoma
* [Increased /decreased] uptake in thyroiditis
- Diffusely increased uptake in Grave’s disease
- Increaseduptake in a solitary nodule in toxic adenoma
- [decreased] uptake in thyroiditis
LABs of Primary vs secondary Hypothyroidism
Primary Hypothyroidism:
* Increased TSH
* Decreased serum T4
Secondary Hypothyroidism:
* Not increased TSH
* Decreased serum T4
Types of Thyroiditis
Chronic Lymphocytic (or Hashimoto) Thyroiditis
Granulomatous (de Quervain) Thyroiditis
Subacute Lymphocytic Thyroiditis
Riedel (Fibrous or Invasive) Thyroiditis
Chronic Lymphocytic (Hashimoto) Thyroiditis.
Linkage to ————— gene cytotoxic
Cytotoxic T-lymphocyte-associated Ag-4
gene (CTLA4)
Microscopic Findings:
* Inflammatory infiltrates (lymphocytes, plasma cells) + Germinal centers
* Atrophic thyroid follicles, lined by Hürthle or Oxyphil cells (marked eosinophil., granular cytopl.)
features of?
Chronic Lymphocytic
(Hashimoto) Thyroiditis
CF of Hashimoto Thyroiditis
Painless, symmetric and diffuse enlargement of the thyroid
complications of Chronic Lymphocytic
(Hashimoto) Thyroiditis
Increased risk for development of B-cell non -Hodgkin lymphomas, within the thyroid gland
causes of Subacute Granulomatous
(de Quervain) Thyroiditis
- Viral infection
- Inflammatory process triggered by viral infections;
commonly, history of upper respiratory tract
infection
Microscopic Findings:
* Disruption of thyroid follicles –> Extravasation of
colloid –> Polymorphonuclear infiltrate –>
Lymphocytes, plasma cells and macrophages
* Development of a granulomatous reaction with
giant cells –> Granulomatous inflammation
* Healing: Resolution of inflammation and fibrosis
Macroscopic features :
- firm gland
- Intact capsule
Features of?
SubacuteGranulomatous
(de Quervain) Thyroiditis
CF of Subacute Granulomatous
(de Quervain) Thyroiditis
- Neck pain (particularly with swallowing)
- Fever
- Malaise
- Transient Hyperthyroidism –> Transient
Hypothyroidism –> Euthyroid state
(within 6-8 weeks)
Macroscopic Features:
* Mild symmetric enlargement of the thyroid gland
Microscopic Findings:
* Lymphocytic infiltrates and hyperplastic germinal centers
Features of?
Subacute Lymphocytic Thyroiditis (aka silent or painless Thyroiditi)
CF of Riedel Thyroiditis (Fibrous/Invasive Thyroiditis)
- Hard and fixed thyroid mass
Microscopic findings:
* Thyroid replaced by fibrous tissue and inflammatory infiltrate (plasma cells , lymphocytes, macrophages)
Features of?
Riedel Thyroiditis
most common casue of Hyperthyroidism?
Grave’s disease
Garve’s diseases coexists with what diseases?
SLE, Pernicious Anaemia (Autoimmune gastritis), DM-t1 and Addison’s disease
Pathogensis of Grave’s disease
caused by the production of IgG autoantibodies directed against the TSH receptor. These antibodies bind to and activate the receptor, causing the autonomous production of thyroid hormones
IgG: Thyroid stimulating immunoglobulin
Macroscopic Features:
* Symmetrical, Diffuse enlargement of the thyroid gland
* Smooth and soft organ
* Intact capsule
Microscopic Findings:
* Diffuse hypertrophy and hyperplasia of the thyroid follicular epithelial cells
* Tall, columnar and crowded epithelial cells
* Small papillae, without fibrovascular cores
* Pale colloid with scalloped margins within the follicular lumen
* Lymphocytes and plasma cells, and germinal
centers
Features of?
Grave’s disease
CF of Grave’s disease
Triad of Manifestations
1) Thyrotoxicosis (all cases)
2) Infiltrative Ophthalmopathy –> Exophthalmos
(40% of cases)
3) Localised Infiltrative Dermopathy or Pretibial
Myxoedema (minority of cases): Scaly thickening and induration of the skin
*Exophthalamos : protruding eyes
Toxic Multi-Nodular Goiter is aka?
Plummer Syndrome
CF of Plummer Syndrome (Toxic Multi-Nodular Goiter)
1) Airway obstruction
2) Dysphagia (difficulty swallowing)
3) Compression of large vessels in the neck and
upper thorax (Superior Vena Cava Syndrome)
Imaging findings of thyroid Follicular Adenomas
1) “warm” or “hot” thyroid nodule –> toxic adenoma
or
2) “Cold” nodules
Macroscopic Features:
* Solitary, spherical lesion
* Well-defined, intact capsule
Microscopic Findings:
* Uniform follicles, containing colloid
* Occasionally, cells with brightly eosinophilic
granular cytoplasm
* Hallmark –> Intact well-formed capsule;
features of?
Follicular Adenoma (aka Hürthle Cell Adenoma)
Macroscopic Features:
cut surface: glassy-appearing, Irregular nodules with variable amounts of brown gelatinous colloid; Areas of fibrosis, haemorrhages, calcification and cystic changes
Microscopic Findings:
* Hyperplastic epithelium (early stages)
* Flattened and cuboidal epithelium with
abundant colloid (periods of involution)
features of?
Multi-Nodular Goiter (Plummer syndrome)
Histo of Hürthle Cell Adenoma (follicular) vs. Carcinoma
Follicular adenoma: intact capsule
Follicular Carcinoma: invades thyroid capsule and vasculature
The 4 major subtypes of Thyroid Carciomas
1) Papillary Carcinoma (>85%)
2) Follicular Carcinoma (5-15%)
3) Anaplastic (Undifferentiated) Carcinoma (<5%)
4) Medullary Carcinoma (5%)
Macroscopic Features:
* Solitary or multifocal lesions
* Variable appearance: Either well-circumscribed
and encapsulated or infiltrative tumors with ill-defined margins
* Possible, areas of fibrosis, calcifications and
cystic changes
* Cut surface: Granular, sometimes with distinct
papillary foci
Microscopic Findings:
* Ground glass or “Orphan Annie eye” nuclei
* Invaginations of the cytoplasm –> Pseudo-inclusions
* Papillary architecture; papillae with dense fibrovascular cores
* Presence of “psammoma bodies”
* Foci of lymphatic invasion
features of?
(Papi and Moma adopted Orphan Annie
Papillary carcinoma
Microscopic Findings:
* Unifrom, small follicles
Macroscopic features:
* Invasion of the thyroid capsule and vasculature
* Possible Hemotogenous spread
features of?
Follicular Carcinoma
Epi of Anaplastic/Undifferentiated carcinomas
Older patients > 65yrs
Quarter of patients –> Past history of a well-differentiated carcinoma (folliclar carcinoma)
Macroscopic Features:
* Bulky mass
* Rapidly enlarging neck mass –> growth beyond thyroid capsule -> Invasion into adjacent neck structures
Microscopic Findings:
* Populations of highly anaplastic cells:
* Large, pleomorphic giant cells or
* Spindle cells with a sarcomatous appearance or
* Mixed spindle and giant cell lesions
* Foci of papillary or follicular differentiation
features of?
Anaplastic Carcinoma
CF of Follicular Carcinoma
- presentation as solitary cold thyroid nodules
- Haematogenous dissemination to the lungs, bones and liver
*important
Medullary Carcinoma are associated with (Type of mutation)?
MEN 2A and 2B (RET mutations)
pathogenesis of Medullary Carcinoma
Neuro-Endocrine Neoplasm
–> from Parafollicular “C cells” of the thyroid
* “C cells” –> produce Calcitonin
Macroscopic Features:
* Solitary nodule or multiple lesions in both lobes
* Multicentricity, common in familial cases
* Areas of necrosis and haemorrhage and extrathyroidal extension (larger tumours)
Microscopic Findings:
* Sheets of Polygonal cells in the Amyloid stroma
* Multi-centric C cell hyperplasia, in familial cases
features of?
Medullary Carcinoma
Immunohistochemistry of Medullary Carcinoma
Intracytoplasmic Calcitonin positivity
CF of Medullary Carcinoma
1) Mass in the neck; possible dysphagia or
hoarseness (sporadic cases)
2) Diarrhoea, caused by the secretion of VIP
*VIP : Vasoactive intestinal Peptide
Diagnosis of Familial cases of Medullary Carcinoma
elevated Calcitonin levels or RET mutations
Genetic predispostion of Primary Hyperparathyroidism
MEN-1 and MEN-2A; Germ-line mutations of MEN-1 and RET, respectively
cause of Hypercalcaemia
1) Hyperparthyroidism (primary, 2,3)
2) Familial Hypercalcaemia
3) Vitamine D toxicity
4) Drugs (Thiazide diuretics)
5) Hypercalcaemia malignancies (Osteolytic metastases, PTH related protein mendiated)
6) Sarcoidosis
7) Immobilisation
Lab findings of Primary Hyperparathyroidism
1) Increased serum ionized calcium (Hypercalcemia)
2) Hypophosphataemia
3) Increased urinary excretion of calcium and phosphate
(Hypercalciuria)
CF of Primary Hyperparathyroidism
- Painful bones
- Renal stones
- Abdominal groans
- Psychic moans
* Stones, Bones, Groans, Psychiatric overtones”
what is Osteitis Fibrosa Cystica
Cystic bone spaces filled w/ Brown fibrous tissue (“Brown tumour”)
Osteitis Fibrosa Cystica is assciated with?
primary Hyperparathyroidism
causes of Secondary Hyperparathyroidism
Renal failure
patho/Lab findings of Secondary Hyperparathyroidism
Chronic renal insufficiency –> Decreased phosphate excretion –> Hyperphosphataemia (↑PO-3) –> Declined serum calcium levels (↓ Ca+2) –> Stimulation of parathyroid gland activity
Macroscopic Features:
* Hyperplastic parathyroid glands
Microscopic Findings:
* Increased number of chief cells, in a diffuse or multinodular pattern
* Decreased number of fat cells (Adipose cells)
* Metastatic calcification in many tissues (e.g.
lungs, heart, stomach, blood vessels)
features of ?
Secondary Hyperparathyroidism
Lab findings of Secondary Hyperparathyroidism
Near normal serum calcium levels
CF of Secondary Hyperparathyroidism
1) Manifestations of Chronic renal failure
2) Metastatic calcification of blood vessels –> Ischaemic damage to skin and other organs (Calciphylaxis)
causes of Tertiary Hyperparathyroidism
Secondary Hyperparathyroidism ->
increased PTH and Ca+2 (HYpercalcemia)
casuses of Hypoparathyroidism
- Surgically removed parathyroids during thyroidectomy
- Congenital absence of parathyroid glands, in conjunction with thymic aplasia (DiGeorge Syndrome)
CF of Hypoparathyroidism
1) Tetany [Chvostek’s sign and Trousseau’s sign]
2) Cardiac arrhythmias w/ and characteristic prolonged QT interval in the ECG
3) Increased intracranial pressure
4) Seizures
Pseudo-Hypoparathyroidism is aka?
Martin-Albright Syndrome
Lab findings of Pseudo-Hypoparathyroidism (Martin-Albright Syndrome)
- low calcium levels
- Elevated levels of phosphate and PTH
Signs and symptoms of Pseudo-Hypoparathyroidism (Martin-Albright Syndrome
- Short stature
- Round face
- Short neck
- Shortened bones in the hands and feet
Lab findings of Primary Adrenal Neoplasms (Adenoma or Carcinoma) or Primary Cortical Hyperplasia (Macro-/ or Micro-nodular)
*Cushing’s Syn.
- ↑ serum Cortisol-levels
- ↓ serum ACTH-levels
Morphology:
Crooked hyaline changes: Accumulation of intermediate keratin filaments in form of homogeneous lightly basophilic material, in cytoplasm of ACTH-producing cells
features of?
Cushing’s Syn. in the pituitary Gland
CF of Cushing’s Syn
1) Truncal obesity
2) “Moon facies”
3) “Buffalo hump”
4) Thinned and easily bruised skin
5) Cutaneous striae in the abdominal region
6) Proximal limb weakness
7) Osteoperosis, with increased susceptibility to bone fractures
8) Hyperglycaemia, glucosuria and polydipsia
(mimicking Diabetes Mellitus)
9) Increased risk for a variety of infections (due to suppressed immune response) - Immunosupression
10) Hirsutism
11) Menstrual abnormalities
12) Mental disturbances (mood swings, depression, frank psychosis)
Macroscopic Features:
* Solitary, small, well-circumscribed lesions
* Cut surface: Bright yellow colour
Microscopic Findings:
* Uniform cells, Admixture of fasciculata and glomerulosa-type cells
* nuclear & cellular pleomorphism
* Eosinophilic, laminated cytoplasmic inclusions (Spironolactone bodies), after treatment with Spironolactone
Syndrome?
Aldosterone-producing Adenomas - Conns Syndrome
* Celluar pleomorphism means that it is not malignant!!!
CF of secondary Hyperaldosteronism
1) Secondary hypertension –> Left ventricular
hypertrophy and increased risk for stroke and
myocardial infarction
2) Hypokalaemia, due to renal potassium wasting –> Muscle weakness, paraesthesias, visual
disturbances, and sometimes tetany
causes of Adreno-Genital Syndromes
* Virilisation syn.
Excess of Androgens caused by:
1) Primary gonadal disorders:
Adrenocortical Neoplasms (CAs > Adenomas)
Congenital Adrenal Hyperplasia (CAH)
patho of Congenital Adrenal Hyperplasia (CAH)
Group of autosomal recessive disorders;
Hereditary defect in an enzyme involved in
adrenal steroid biosynthesis, commonly
Cortisol –> Decreased Cortisol levels –>
Increased ACTH secretion –> Adrenal
Hyperplasia –> Increased production of
Cortisol precursor Steroids –> Synthesis of
Androgens –> Virilising Syndrome
———– :Most common enzymatic defect <> 21-Hydroxylase deficiency; mutation in the CYP21A2 gene
Congenital Adrenal Hyperplasia (CAH)
Morphology :
* Bilateral Hyperplastic Adrenals
* Thickened, nodular and brown Adrenal Cortex
* Mainly, compact, eosinophilic, lipid depleted cells, intermixed with a variable number of lipid-laden clear cells
Syndrome?
Congenital Adrenal Hyperplasia (CAH)
Adrenal Insufficiency Examples
- Primary Acute Adrenocortical Insufficiency
(Adrenal Crisis) - Primary Chronic Adrenocortical Insufficiency
(Addison Disease) - Secondary Adrenocortical Insufficiency
causes of Acute Adreno-Cortical Insufficiency (Adrenal Crisis)
1) Massive Adrenal haemorrhage:
* Waterhouse-Friderichsen Syndrome
(overwhelming sepsis caused by Neisseria meningitidis)
* Patients under anticoagulant therapy
* Disseminated Intravascular Coagulation (DIC)
2) Rapid withdrawal of steroids or failure to
corticosteroid therapy
3) Failure to increase steroid doses in response to
an acute stress
Causes of primary Chronic Adreno-Cortical
Insufficiency (Mb. Addison)
1) Autoimmune Adrenalitis (immune system attacks the adrenals)
2) Primarily, metastatic carcinomas from the lung and breast
3) Infections and immune deficiency states: Tuberculosis, Patients with AIDS; Adrenal insufficiency from infectious (e.g. CMV) and non-infectious complications (e.g. Kaposi Sarcoma) of their
disease
* CMV : cytomegalovirus
LAB findings of Secondary Adreno-Cortical Insufficiency
- Low serum ACTH
- Marked rise in plasma Cortisol levels, caused by
exogenous ACTH administration
Adreno-Cortical Carcinomas Inherited causes
i. Li-Fraumeni Syndrome
ii.Beckwith-Wiedemann Syndrome
Macroscopic Features:
* Large, invasive lesions
* Cut surface: Poorly demarcated masses, with
necrosis, haemorrhage and cystic changes
* Alveolar pattern of growth
Microscopic Findings:
* Well-differentiated cells (similar to those of
Adenomas) or bizarre pleomorphic cells
* Few intranuclear “pseudo-inclusions”
Syndrome?
Adreno-Cortical Carcinomas
What Neoplasms synthesize and release
Catecholamines ?
* Catecholamines are released by Chromaffin cells
Pheochromocytoma
“rule of 10s” of Pheochromocytoma
- 10% of Pheochromocytomas —> Extra-Adrenal; occurrence in the organ of Zuckerkandl and the Carotid body (named Paragangliomas)
- 10% of Adrenal Pheochromocytomas -> Bilateral
- 10% of Adrenal Pheochromocytomas -> Malignant
- 10% of Adrenal Pheochromocytomas -> Not
associated with Hypertension
Familial cases:
25% of patients with Pheochromocytomas and Paragangliomas –> have Germline mutations in one of the 4 genes, what are they?
- RET –> MEN Type 2 syndrome
- NF1 –> Neurofibromatosis Type 1 syndrome
- VHL –> Von Hippel Lindau disease
- SDHB, SDHC and SDHD
Macroscopic Features:
a. Small, circumscribed lesions that compress
the adjacent adrenal or
b. Large, haemorrhagic, necrotic and cystic
masses that destroy the adrenal gland
Microscopic Findings:
* Polygonal to spindle-shaped Chromaffin cells and the Sustentacular cells –> Formation of “Zellballen”, with a rich vascular network
* Finely granular cytoplasm
* Quite pleomorphic nuclei*
* Capsular and vascular invasion
Syndrome?
Pheochromocytoma
*
Stain/ tests used in the detection of Pheochromocytoma
Chromogranin A (Tumour marker) , S-100 (stain)
CF of Pheochromocytoma
-
Hypertension (abrupt elevation of BP, together
with tachycardia, palpitations, headache, sweating and tremor) - Abdominal and/or chest pain
- Nausea and vomiting
Lab findings of Pheochromocytoma
Increased urinary excretion of free Catecholamines and their metabolites
*
Immunohistochemistry detection of Neuroblastoma of the Adrenal Medulla
Neuron Specific Enolase
(NSE), Synaptophysin
**
Micro of Ganglio-Neuroblastomas vs Ganglio-Neuromas
Ganglio-Neuroblastomas:
- Ganglion cells,
- Neuroblasts (Primitive appearing cells),
- “Schwannian stroma”
Ganglion-Neuromas:
- Ganglion cells ,
- “Schwannian stroma”
Factors that influence the prognosis of Neuroblastoma
1) Age : children <18 months (better prognosis than older ones)
2) Stage of the tumour
3) Morphology: “Schwannian stroma” andGangliocytic differentiation –> Favourable histologic pattern (Ganglio-neuromas/Ganglio-neuroblastoma)
4) NMYC Amplification: The greater the number of
copies, the worse the prognosis; Most important
genetic abnormality; Independent factor for
rendering a tumour as “high” grade, irrespective
of stage or age, irrespective of stage or age
5) Disseminated Neuroblastomas in neonates –>
Multiple cutaneous metastases (characteristic
deep blue discolouration of the skin, known as
“blueberry muffin baby”)
Lab findings of Neuroblastomas
- Elevated blood levels of Catecholamines
- Elevated urine levels of Catecholamine metabolites (Vanillyl-Mandelic Acid [VMA] and Homo-Vanillic Acid [HVA])
**
What tumour causes characteristic deep blue discoloration of the skin, known as “blueberry muffin baby”
Neuroblastoma of the Adrenal Medulla
Adreno-cortical Carcinomas are Associated w/ ———-
Virilisation
Celluar Components of the Adeno-Hypophysis (Anterior pituitary)
basophilic, eosinophilic and
chromophobic cytoplasm
Cause of Hyperpituitarism
*Excessive secretion of trophic hormones
Anterior Pituitary Aden.
Complictions of Pituitary Adenoma
i. Visual field defects (bitemporal hemianopsia),
ii. Elevated intra-cranial pressure (headache, nausea, vomiting),
iii. Seizures or obstructive hydrocephalus
iv. Pituitary apoplexy (acute haemorrhage in an Adenoma)
Genes involved in the development of familial Pituitary Adenomas (Prolactinoma)?
MEN 1, CDKNIB, PRKARIA
and AIP
Microscopic Findings:
* Uniform, polygonal cells arranged in sheets, cords or papillae
* Uniform or pleomorphic nuclei (Monomorphic
appearance of tumour cells)
* Low mitotic index
* Acidophilic, basophilic or chromophobic cytoplasm
* Sparse supporting connective tissue or reticulin
* Small round cells
* Small round nuclei
* Pink to blue cytoplasm
PITUITARY ADENOMAS (Anterior)
Epi of Prolactinomas
Most common type of functional
Pituitary Adenomas
CF of Prolactinomas
- Hyperprolactinaemia
- Amenorrhoea
- Galactorrhoea
- Loss of libido
- Infertility
What is Pituitary Stalk effect ?
Hyperprolactinaemia caused by a mass
(other than Prolactinoma) in the supra-sellar
compartment –> which inhibits the normal inhibitory influence of Hypothalamus on Prolactin secretion
Microscopic features:
* Chromophobic cells (clear cells)
* Sphaerical microcalcifications
Prolactinomas
Epi of Growth Hormone-Producing
(Somatotroph) Adenomas
Second most common type of
functional Pituitary Adenomas
Microscopic features:
* Densely or sparsely granulated cells
* Paranuclear “fibrous body”
Growth Hormone-Producing (Somatotroph) Adenomas
*Paranuclear bodies = indication of Pituitary adenomas
* GH-Producing (Somatotroph) Adenomas
Overproduction and release of GH leads to hepatic
secretion of —— –>
–> In cases of prepubertal children (before closure of epiphyses) —-> —————–
–> After closure of epiphyses –> ————–
secretion of IGF-1
Before –> Giganitism
After (adults) –> Acromegaly
CF of Growth Hormone-Producing
(Somatotroph) Adenomas
- Gigantism or Acromegaly
- Abnormal Glucose tolerance
- Diabetes Mellitus
- Generalised muscle weakness
- Hypertension
- Arthritis
- Osteoporosis
- Congestive Heart Failure
Epi of ACTH-Producing Adenomas
- Commonly, Micro-Adenomas
- Clinically silent or manifested as Cushing Syndrome
Cause of Nelson Syndrome
Development of large (Macro-adenomas), aggressive ACTH Adenomas, after removal of both Adrenal Glands,
for treatment of Cushing Syndrome
CF of Nelson Syndrome
i. Hyperpigmentation of the skin,
ii. Headaches and
iii. Vision impairment
Lab findings of Nelson Syndrome
↑ levels of ACTH and
β-MSH
CF of Gonadotroph (FSH- and LH-producing) Adenomas
- Impaired vision,
- headaches,
- diplopia (double vision),
- pituitary apoplexy
Immunohistochemistry of Gonadotroph (FSH- and LH-producing) Adenomas
+ve for : common Gonadotropin α-subunit , the specific β-FSH and β-LH subunits
CF of Non-functional Pituitary Adenomas
- Typical presentation of mass effects
- Compromise of the residual Anterior
Pituitary –> Hypopituitarism
Microscopic features:
Rosettes of small cells
Monomorphic (pleomorphic) chromatin-rich nuclei
Null-Cell Adenomas (aka Hormone-negative adenomas)
*Null-cell adenomas have abscense of immuno-histochemical reactivity
Causes of Hypopituitarism
1) Hypopituitarism, accompanied by Diabetes
Insipidus, is almost always of hypothalamic
origin
2) Non-functioning Pituitary Adenomas
3) Ablation of the Pituitary Gland by surgery or irradiation
4) Inflammatory disorders (e.g. Sarcoidosis, Tbc),
5) trauma and metastatic neoplasms
6) Sheehan’s syndroms or postpartum necrosis of Anterior Pituitary Gland
7) Other causes of ischaemic necrosis: DIC, sickle cell anaemia, trauma, shock, etc.
CF of Hypopituitarism (depending on hormone(s) lacking)
- GH-deficiency –> —–
- GnRH deficiency –> ——- (F); —— (M)
- PRL deficiency –> ———-
- TSH deficiency –> ——–
- ACTH deficiency –> ———
- GH-deficiency –> Dwarfism (in children)
-
GnRH deficiency–> Amenorrhoea and Infertility
(F); Decreased Libido and Impotence (M) - PRL deficiency –> Failure of postpartum Lactation
- TSH deficiency –> Hypo-Thyroidism
- ACTH deficiency –> Hypo-Adrenalism
*GnRH: Gonadotropin-Releasing Hormone
causes of Empty sella Turcica
- Pituitary compression through herniation of the Arachnoidea (Arachnoid mater)
- Sheehan syndrome
- Total infarction of an Adenoma
- Operation or Radiation of the Hypophysis
Posterior Pituitary Syndromes examples
1) Central Diabetes Insipidus
2) Syndrome of Inappropriate ADH (SIADH) secretion
* Posterior Pituitary Syndromes
CF of Syndrome of Inappropriate ADH (SIADH) secretion
- Cerebral oedema –> Neurologic dysfunction
- Normal blood volume and NO peripheral oedema
* Posterior Pituitary Syndromes
Lab findings of Central Diabetes Insipidus
Increased serum Sodium and osmolality, as a result of excessive renal loss of free H2O
MEN-1 loc+ examples
- 1) parathyroid –> Primary Hyperparathyroidism, due to Hyperplasia or Adenoma; Most common
manifestation in MEN-1 (80-95% of cases)
2) Pituitary –> Prolactinoma (Prolactin-secreting Macroadenoma)
3) Pancrease –> *insulinomas** (zollinger Elison syndrome)
MEN-2
All persons with germ-line RET mutations should
undergo prophylactic thyroidectomy to prevent the unavoidable development of ?
Medullary
Carcinomas
Loc of MEN-2A +examples
1) Thyroid: Medullary Carcinomas
2) Adrenal Medulla –> Pheochromocytomas;
3) Parathyroid: 10-20% of patients –>
Development of Parathyroid Gland Hyperplasia
–> Primary Hyperparathyroidism
MEN-2B involves?
Thyroid (Medullary carcinoma) and the Adrenal Medulla (pheochromocytoma)
Thyroid and Adrenal Medulla disease shows
similarities to MEN-2A, with the following
differences:
* MEN-2B patients do not develop Primary
Hyperparathyroidism
* Extra-endocrine manifestations in MEN-2B
patients:
* Ganglio-Neuromas of mucosal sites
(GI tract, lips, tongue)
* Marfanoid habitus
