Endocrinology - Dr Niamh Conlon and Dr Linda Feely PDF

Preview

Summary

Dr Niamh Conlon and Dr Linda Feely ...

Description

HPA axis:  Represents interaction between the hypothalamus, pituitary and the adrenal glands HPT axis:  Represents interaction between the hypothalamus, pituitary and the thyroid glands *parvicellular neurones that secrete hormones from the hypothalamus

Pituitary Anterior pituitary hormones 1. FSH 2. LH 3. ACTH 4. TSH 5. Prolactin 6. Endorphins 7. GH

FLAT PEG – FSH, LH, ACTH, TSH, ENDOCRINOLOGY Prolactin, Endorphins, GH

Posterior pituitary 1. ADH (vasopressin) – made in hypothalamus, stored in pituitary 2. Oxytocin o Uterine SM contraction o Expulsion of milk  Deficiency –> diabetes insipidus  Excess –> SIADH Pituitary Neoplasms  Mostly small incidental adenomas  Carcinomas rare  Metastases from breast, lung, GIT *pituitary adenoma is the most common cause of hyperpituitarism Pituitary Adenomas  Prolactinomas  GH adenomas  ACTH adenomas Hypopituitarism (ant pituitary)  Often due to pressure effects of neoplasm, pituitary apoplexy  Diagnosis: o Low serum corticosteroid levels  Usually gonadotrophins effected first, then TSH & ACTH

Thyroid Gland Goitre  Any visible/palpable enlargement of the thyroid gland  Due to impaired synthesis of thyroid hormones o Dietary iodine deficiency most common cause  2 types o Diffuse non-toxic (simple) o Multi nodular Hyperthyroidism/Thyrotoxicosis  Palpitations  Weight loss ENDOCRINOLOGY  ↑ appetite  Decreased heat tolerance *everything speeds up  Elevated T3, T4  Low TSH Causes:  Graves disease  Multinodular goitre with toxic nodule  Toxic adenoma Graves Disease  Hyperthyroidism with diffuse enlargement of the  Anti TSH receptor antibodies  Exophthalmos  Pretibial myxodema o Localised lesions of the skin from deposition hyaluronic acid

   

Diarrhoea Arrhythmias Osteoporosis Exophthalmos

Hypothyroidism  Depression  Slowing of physical and mental  Muscle aches and weakness activity  Dry and scaly skin  Tiredness, sensitive to cold  Weight gain, constipation *everything slows down  Cretinism – severe hypothyroidism in children  Low T3 and T4  Elevated TSH Causes:  Hasimoto’s  Surgery  Radioactive iodine  Severe iodine deficiency

gland

of

Hashimotos thyroiditis  Painless enlargement of the gland (early) o Symmetric and diffuse  Fibrosis results in shrunken gland (late) Thyroid neoplasms  Adenoma o Follicular  Carcinoma o Follicular o Papillary o Medullary o Anaplastic  Lymphoma  Metastases

ENDOCRINOLOGY

Follicular adenoma  Solitary nodule  Completely encapsulated Follicular carcinoma  Capsular invasion Papillary carcinoma Follicular carcinoma  Vascular invasion  Blood spread  Lymph node spread  Spread o Vascular: lung, bone, liver, brain  Treatment o Surgery, iodine 131, thyroxine Papillary carcinoma Treatment the same for follicular and  Nuclear features papillary o Enlargement o Irregularity of nuclear membrane o Psammoma bodies  Regional lymph node metastases  Blood spread uncommon  Treatment o Surgery, iodine 131, thyroxine Medullary Carcinoma  5-10% thyroid malignancies  Arises from neuroendocrine cells  Elevated calcitonin  Spread to lymph nodes, lung, liver and bone  50% fatality Anaplastic Carcinoma  Undifferentiated



Fatality 95%

Molecular diagnostics for thyroid neoplasms 1. BRAF – point mutation 2. RAS – point mutation 3. RET/PTC – rearrangement 4. PAX8-PPARγ – rearrangement *20% adenomas have RAS mutation, 40-50% of follicular carcinomas

Parathyroid glands Parathormone  ↑ blood Ca levels ENDOCRINOLOGY o Absorption from GIT & reabsorption from kidneys  ↑ resorption of bone  ↑ urinary excretion of PO4 Hyperparathyroidism Primary  Adenoma or hyperplasia  Elevated PTH and Ca  Asymptomatic or o Osteoporosis o Renal calculi o Nausea, constipation, peptic ulceration, chronic pancreatitis o Depression Secondary  Due to renal failure  Ca normal, elevated PTH  Response to hypocalcaemia Tertiary  Autonomous production of PTH  Elevated Ca and PTH Hypoparathyroidism  Causes: o Autoimmune o Post-surgery o Familial o Congenital absence of glands  Low Ca & PTH Tetany

Bones Stones Groans Moans



 

Chvostek’s sign o Tapping of facial nerve Chvostek’s sign – Cheek causes contraction of facial Trousseau’s sign – Tight in cuff muscle Trousseau’s sign o Occlusion of brachial artery with BP cuff triggers carpal spasm Both as result of hypocalcaemia

Diabetes mellitus Type 1  Caused by autoimmune destruction of islet β-cells o Cytotoxic effect and release of toxic ENDOCRINOLOGY cytokines  HLA-DR3 & HLADR4  Young patients with normal BMI Presents with o Polydipsia o Polyuria o Blurred vision o DKA  Insulin therapy Diabetic Ketoacidosis  Excessive serum ketones  Arises with stress – infection o Epinephrine releases glucagon secretion  This increases lipolysis o Increased lipolysis increases FFAs which are converted to ketone bodies  Results in: o Hyperglycaemia o Anion gap metabolic acidosis o Hyperkalaemia  Presents with o Dehydration o Nausea, vomiting o Mental state changes o Fruity smelling breath  Treatment o Fluids, insulin and replacement of electrolytes Type 2  Insulin resistance o Associated with obesity  β-cell dysfunction o Overcompensate at first

 Hypertrophy and hyperplasia of β-cells o Subsequent deficiency due to hypotrophy and hypoplasia, amyloid deposition  Middle aged patient with sedentary lifestyle, overweight, comorbidities Complications of DM Non-enzymatic glycosylation of vascular BM  NEG of large and medium arteries leads to atherosclerosis o CVD o PVD  Amputation  NEG of small vessels leads to hyaline arteriosclerosis o Leads to glomerulosclerosis  Small scarred kidneys ENDOCRINOLOGY with granular surface o Preferential involvement of efferent arterioles leads to hyperfiltration injury with microalbuminuria  Progresses to nephrotic syndrome, characterised by KimmelsteinWilson nodules Osmotic damage  Glucose freely enters schwann cells, pericytes of retinal vessels and the lens  Glucose converted to sorbitol which causes osmotic damage o Leads to peripheral neuropathy o Impotence o Blindness o Cataracts  Hyperosmotic Non ketotic Coma o Older T2 DM patients o Precipitated by infection, dehydration o Due to reduction in ECF o Reduction in consciousness o Requires fluid resuscitation with K+ and insulin

Adrenal gland Cortex  Glucocorticoids  Mineralocorticoids  Androgens Medulla  Catecholamines

S-S-S Sugar – glucocorticoids Salt – mineralocorticoids Sex - androgens

Adrenal cortex – hypofunction Primary Acute  Waterhouse-Friderichsen Syndrome

o Haemorrhagic necrosis due to DIC in young children with N meningitidis o Lack of cortisol, exacerbates hypotension leading to death Chronic  Addison’s disease o Progressive destruction of adrenal glands o Hyperpigmentation - excess ACTH by products stimulates melanocytes o Hypotension o Hyponatremia, hyperkalaemia,

Addison’s Disease – Adrenal Atrophy and Absence of hormone production

ENDOCRINOLOGY hypovolaemia Secondary  Pituitary/hypothalamic disease  Long term steroid use Distinguishing features from Primary  Lack of hyperpigmentation  Normal aldosterone synthesis o Hyponatremia and hyperkalaemia not features  Low levels serum ACTH and cortisol  Rise in serum cortisol after exogenous ACTH admin Adrenocortical Hyperfunction Cushings Syndrome  Excess cortisol  Muscle weakness  Moon facies, buffalo hump and truncal obesity  Abdominal striae  Hypertension  Causes: o Exogenous corticosteroids o Primary renal adenoma, hyperplasia or carcinoma o ACTH-secreting pituitary adenoma o Ectopic ACTH secretion by neoplasm eg of lung  Treatment o High dose dexamethasone supresses ACTH production by pituitary adenoma Hyperaldosteronism Primary  Usually caused by cortical adenoma  Hypokalaemia, hypernatremia, increased urinary loss of K+  Oedema

 Hypertension Secondary  Activation of RAAS  Arterial hypovolaemia o Cardiac failure o Nephrotic syndrome Adrenal Neoplasms Cortex  Adrenocortical Adenoma o Small, well circumscribed o No ENDOCRINOLOGY

invasion of fat, vasculature

o Minimal mitotic activity, no necrosis  Adrenocortical carcinoma o Large o Necrosis & haemorrhage o Infiltrates adjacent tissue o Invades capsule and lymphovascular space Medulla  Neuroblastoma o Majority < 5 years of age o Highly malignant o Prognosis related to age  Gets worse as get older  Phaeochromocytoma o Catecholamine producing tumour o Presentation  Hypertension, palpitations o Associated with von Hippel-Lindau disease Multiple Endocrine Neoplasia’s  Autosomal Dominant MEN1  Loss of function  Pituitary, parathyroid, pancreas  Will often have kidney stones and ulcers MEN2  Protoonco-gene o RET  Tyrosine kinase  MEN2A o Medullary thyroid carcinoma, phaeochromocytoma, parathyroid tumours



MEN2B o MTC, Phaeo, oral/intestinal neurofibromas o Often present with marfanoid habitus  Long limbs, hyperlaxity of joints

ENDOCRINOLOGY...