Hypothyroidism Pathophysiology, differentials, investigations and management. Quiz Cases Dr Azeem Alam, MBBS BSc (Hons) Surgical AFP Guy’s and St. Thomas’ Hospital Endocrinology series Content reviewed on the 26/04/2020.
Case 1 History A 36-year-old Caucasian female presents to her GP in London with ongoing fatigue. She has also gained a significant amount of weight and has been constipated recently. She looks tired and you note that she is wearing a woolly hat, despite it being a warm, summer’s afternoon. Observations HR 56, BP 126/84, RR 16, SpO 2 98%, Temp 37.4°C. 2
Case 1 History A 36-year-old Caucasian female presents to her GP in London with ongoing fatigue. She has also gained a significant amount of weight and has been constipated recently. She looks tired and you note that she is wearing a large coat, despite it being a warm, summer’s afternoon. Observations HR 56, BP 126/84, RR 16, SpO 2 98%, Temp 37.4°C. 4
Aetiology Pathophysiology Definition: a deficiency in circulating thyroid hormone. Thyroxine (T4) and tri- iodothyronine (T3). 6
Aetiology Primary hypothyroidism • 95% of cases • Iodine deficiency • Autoimmune thyroiditis • Transient thyroiditis TSH Free T4 Primary hypothyroidism ↑ ↓ Overt hypothyroidism Subclinical ↑ ↔ hypothyroidism 8
Aetiology Primary hypothyroidism Features Iodine deficiency Commonest cause worldwide Hashimoto’s thyroiditis Commonest cause in the developed (autoimmune) world • Autoimmune (anti-TPO antibodies) • Diffuse painless goitre • Transient thyrotoxic state, hashitoxicosis • Increased risk of non-Hodgkin lymphoma • Viral prodrome Subacute (De Quervain’s) • Transient thyrotoxic state thyroiditis (transient) • Painful goitre • Raised inflammatory markers 9 • Self-limiting
Aetiology Categorisation Causes • Iodine deficiency Primary hypothyroidism • Autoimmune thyroiditis • Transient thyroiditis • Drugs • Post-ablative therapy or surgery • Infiltrative disorders • Congenital 10
Secondary hypothyroidism Aetiology Secondary (central) hypothyroidism • Pituitary or hypothalamic disorder TSH Free T4 ↓ or ↔ ↓ Secondary hypothyroidism 12
Aetiology Categorisation Causes • Pituitary adenoma or glioma Secondary hypothyroidism (central) • Pituitary surgery or radiation • Vascular disorders • Pituitary apoplexy • Sheehan syndrome • Hypothalamic disorders • Infiltrative disorders • Drugs 13
Epidemiology Prevalence of any cause of hypothyroidism is 1-2%, with Hashimoto’s thyroiditis being the most common cause. • Female gender : 15-20x more frequent • Middle-aged: peak age is 30-50 years old • Family history • History of autoimmunity : e.g. pernicious anaemia or T1DM • Chest or neck irradiation • Thyroidectomy or radioiodine 14
Clinical features Symptoms Signs Weight gain Bradycardia Cold intolerance Goitre Lethargy Loss of lateral aspect of eyebrows Dry skin Hair loss Constipation Hyporeflexia Menorrhagia: later develop oligomenorrhoea and amenorrhoea 15
Clinical features (1) 16
Investigations: stable patient Primary investigations: • TFTs : decreased T3/T4 and increased TSH in primary hypothyroidism • Antibodies : anti-TPO antibodies associated with Hashimoto’s thyroiditis (95%) • Inflammatory markers : raised in De Quervain’s thyroiditis Investigations to consider: • Ultrasound : if there is a goitre or focal nodule and malignancy is suspected • Radionucleotide scan : not routine • FBC and serum B12 level : assess for possible pernicious anaemia • Fasting lipids : hypothyroidism is associated with hypercholesterolemia • Serum glucose and HbA1c : hypoglycaemia and T1DM • Coeliac serology : assess for coeliac disease 17
Investigations: autoantibodies Thyroid autoantibodies Autoantibody Condition Prevalence Anti-TSH receptor Graves’ disease 90-100% Hashimoto’s thyroiditis 0-5% Anti-TPO Graves’ disease 70-80% Hashimoto’s thyroiditis 90-95% Anti-thyroglobulin Graves’ disease 20-40% Hashimoto’s thyroiditis 30-50% 18
Management Overt hypothyroidism: • Levothyroxine (T4): offer levothyroxine with regular review of symptoms and TSH every 3 months Subclinical hypothyroidism: • Depends on the age, symptoms and TSH [3] • TSH > 10 mU/L and normal T4: consider levothyroxine • TSH < 10 mU/L and normal T4: consider 6 month trial of levothyroxine if symptomatic and < 65 years old • In all other cases observation is indicated 20
Myxoedema coma • Extreme manifestation of hypothyroidism • > 60 years old • Causes : hypothermia, infections (e.g. influenza), medication (e.g. amiodarone), surgery, trauma Symptoms Signs Long-standing hypothyroid symptoms Bradycardia and hypotension CNS : confusion, psychosis, Hypothermia : often < 35.5°C apathy Constipation Myxoedematous face Hypoventilation 23
Myxoedema coma: investigations Bedside • ECG : bradycardia Bloods • TFTs : raised TSH and reduced T4 • FBC : normocytic normochromic anaemia • U&Es : hyponatraemia and deranged renal function • ABG : hypoxia, hypercapnia, respiratory acidosis • Blood glucose : hypoglycaemia • Infection screen Investigations to consider : • Lipid profile : hyperlipidaemia • Serum cortisol : exclude adrenal insufficiency 24
Myxoedema coma: management General measures • ITU or HDU • NIV or mechanical ventilation: may be required • Correct hypoglycaemia and electrolyte disturbances • Slow warming Specific measures • IV thyroid hormone replacement : often levothyroxine alone (100-500 μ g), but controversial • Antibiotics : many advocate broad-spectrum antibiotics • IV hydrocortisone : assume adrenal insufficiency until excluded (100 mg) Mortality : 50% even if promptly treated Poor prognosis : elderly, hypothermic and bradycardic 25
Top decile question 26
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References 1. Herbert L. Fred, MD and Hendrik A. van Dijk / CC BY (https://creativecommons.org/licenses/by/2.5) 29
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