Updated review Common thyroid conditions Thamer Alessa, MD, FACE, - PowerPoint PPT Presentation

Updated review Common thyroid conditions Thamer Alessa, MD, FACE, CCD Endocrinology, Diabetes & Metabolism Jaber Al-Ahmad Hospital/Dasman Diabetes Institute

Case 1 • A 49-year-old woman presented to saturation 90% on room air ER, with progressive lethargy and dyspnea (NYHA functional class IV) • Examination: – Cool, dry skin • Has a 1-yr h/o weight gain, hair loss, – Pretibial, periorbital and bilateral dry skin, constipation, cold lower extremity non-pitting edema intolerance and leg swelling – Thyroid not palpable – CV: muffled heart sounds, S3 and grade 2/6 systolic ejection murmur at • Vital signs: the apex radiating to the left axilla – Temp 31.1°C, BP 134/ 83 mmHg, HR – Lung examination: rales bilaterally 88 bpm, RR 18 breaths/min and O 2

Case 1 • Transthoracic echocardiography: showed a markedly dilated LV with a diastolic dimension of 5.7 cm, a severely depressed LVEF of 15 – 20%, severe diffuse hypokinesis, a moderate to severe degree of MR and a small pericardial effusion

Case 1 – Laboratory • TSH 52 mIU/L (0.27-4.2 uIu/mL) • FT4 2.3 pmol/L (7.8-16 pmol/L) • TPO antibody titre 287 IU/mL (<40)

Case 1 • What is the most likely diagnosis? Myxedema Coma

Myxedema Coma • The most severe stage of hypothyroidism: – Impaired sensorium, hypoventilation, bradycardia, hypotension & hypothermia – Cardiovascular collapse and shock – Rare, high mortality rate (25-50%) • Occurs usually in patients with long-standing, undiagnosed hypothyroidism. • Precipitated by: – Infections – Trauma, surgery – Exposure to cold – Cardiovascular conditions (MI, stroke) – Drugs

Diagnostic Criteria of Myxedema Coma Total score: • >60 highly suggestive/diagnostic of myxedema coma • 25-59 supportive of diagnosis of myxedema coma • <25 myxedema coma unlikely Score 80 Adapted from Popoveniuc G, et al. Endocr Pract 2014; 11:1-36

CV Complications of Untreated Hypothyroidism • Dyslipidemia • Atherosclerotic cardiovascular disease • Congestive heart failure • Reversible cardiomyopathy (severe hypothyroidism) Modified from ATA 2014

Heart Failure Events by TSH risk risk Gencer Circulation 2012; 126:1040

Hypothyroidism and CVS effects Tissue Systemic Vascular Thermogenesis Resistance T 4 T 4 Diastolic Blood Pressure T 3 T 3 Cardiac Output Renin/ Angiotensin/Aldosterone System Preload Cardiac Chronotropy, Afterload Inotropy, & Lusiotropy Based on Klein and Danzi, In: The Thyroid 2004

Hypothyroidism and CVS effects Tissue Systemic Vascular Thermogenesis Resistance T 4 T 4 Diastolic Blood Pressure T 3 T 3 Cardiac Output Renin/ Angiotensin/Aldosterone System Preload Cardiac Chronotropy, Afterload Inotropy, & Lusiotropy Based on Klein and Danzi, In: The Thyroid 2004

Other Manifestations of Myxedema Coma • Neurologic – Patients might manifest variable degrees of altered consciousness – Brain function is affected by reduction in oxygen delivery and subsequent consumption, decreased glucose utilization, reduced cerebral blood flow and hyponatremia • Pulmonary – Hypoventilation is common, results from central depression of ventilatory drive with decreased responsiveness to hypoxia and hypercapnia – Other contributing factors to hypoventilation: • Respiratory muscle weakness, mechanical obstruction by a large tongue, and obesity- hypoventilation syndrome – Fluid accumulation may cause pleural effusions and decreased diffusing capacity

Other Manifestations of Myxedema Coma • Renal – Function may be compromised with reduced GFR due to low cardiac output and peripheral vasoconstriction or rhabdomyolysis – Hyponatremia is common, caused by increased serum ADH and impaired water excretion • Gastrointestinal – The GI tract can be marked by mucopolysaccharide infiltration and edema – Neuropathic changes can cause malabsorption, gastric atony, paralytic ileus, and megacolon – Ascites may occur due to increased capillary permeability or heart failure – GI bleeding secondary to an associated coagulopathy may occur • Hematologic – Associated with coagulopathy (acquired von Willebrand syndrome type 1 and decreases in factors V, VII, VIII, IX, and X) and anemia

Management • Initial steps: – Airway management • Mechanical ventilation commonly required during the first 36-48 hours • Some patients require prolonged respiratory support for as long as 2-3 weeks – Thyroid hormone replacement – Glucocorticoid therapy – Supportive measures • For hypothermia, hypoventilation, hyponatremia, volume depletion and hypoglycemia

Thyroid hormone replacement ATA 2014 • Initial thyroid hormone replacement for myxedema coma should be levothyroxine and liothyronine given intravenously. • Levothyroxine: – Loading dose of 200 – 400 µ g – Daily replacement dose of 1.6 µ g/kg body weight (reduced to 75% if given IV) – Oral therapy may be instituted after the patient improves clinically • Liothyronine: – Loading dose of 5 – 20 µ g, followed by a maintenance dose of 2.5 – 10 µ g every 8 hours – Therapy can continue until the patient is clearly recovering

Glucocorticoid therapy ATA 2014 • Empiric glucocorticoid coverage should be employed as part of the initial therapy for myxedema coma, with intravenous glucocorticoid administration, at doses appropriate for the stressed state, preceding levothyroxine administration.

Case 2 • A 53 year old retired • Vital signs: Temp 36.1 o C, pulse housewife complains of 58 bpm, BP 140/100 mmHg progressive weight gain (7 kg • Physical exam: in 1 yr) and fatigue, started – Moderately obese with pale, 1.5 years ago cool, dry skin – Thyroid gland slightly enlarged, firm, not nodular, mobile, and • Complains from poor sleep not tender quality and lack of energy to – Deep tendon reflex delayed workout

Case 2 - Laboratory tests • CBC and differential WBC are normal • Free T4 9.8 pmol/L (7.8-16) • TSH 7.2 uU/ml (0.27-4.2 uIu/mL) • TPO Ab 150 IU/mL (<2.0) • Total cholesterol is 7.1 mmol/l • HDL-C 1.01 mmol/l • TG 1.82 mmol/l • LDL-C 5.2 mmol/L

Case 2 • What is the likely diagnosis? Subclinical hypothyroidism

Case 2 • Most common causes of subclinical hypothyroidism: – Autoimmune thyroid disease (Hashimoto's thyroiditis) – Radioactive iodine therapy for hyperthyroidism – Thyroidectomy – External beam radiotherapy

Case 2 • Any additional tests required to help confirm the diagnosis? No Thyroid autoantibodies are arguably insensitive and the cost does not justify the benefit Thyroid autoantibodies helpful to predict the risk of developing overt hypothyroidism in patients with subclinical hypothyroidism ATA 2014

Case 2 • Is treatment with thyroid replacement therapy is indicated in this patient with subclinical hypothyroidism? Depending on risk factors

Complications of Untreated Hypothyroidism • Dyslipidemia • Atherosclerotic cardiovascular disease • Congestive heart failure • Reversible cardiomyopathy (severe hypothyroidism) ATA 2014

Hypothyroidism and dyslipidemia • Laboratory abnormalities: – Elevated total cholesterol – Elevated LDL-C – Elevated apolipoprotein B – Elevated Lp (a) (thrombogenic and atherogenic) – HDL2 (apo A1) increased – Elevated triglycerides – Raised homocysteine, CRP, urate, phosphate

Hypothyroidism and dyslipidemia Colorado hypothyroidism prevalence study. Canaris et al 2000

Hypothyroidism and dyslipidemia Thyroid hormone: • ↑ LDL receptor expression • ↑ CETP concentrations • ↑ hepatic lipase (HL) concentrations • ↑ hepatic cholesterol synthesis by inducing HMG CoA reductase • ↓ intestinal cholesterol absorption an action mediated by the Niemann-Pick C1-Like 1 (NPC1L1) protein The reverse occurs in hypothyroidism Elizabeth N. Pearce; The Journal of Clinical Endocrinology & Metabolism 2012, 97, 326-333

Subclinical Hypothyroidism Impact on IHD Events Biondi, Cooper Enocr Rev 2008 Feb;29(1):76-131

Subclinical Hypothyroidism and CHD or Mortality Ochs N, et al. Ann Intern Med. 2008 Jun 3;148(11):832-45.

Subclinical Hypothyroidism and CHD or Mortality Ochs N, et al. Ann Intern Med. 2008 Jun 3;148(11):832-45.

Stratified Analysis of the Association of Subclinical Hypothyroidism with Risk for CHD Ochs N, et al. Ann Intern Med. 2008 Jun 3;148(11):832-45.

HRs for CHD Events, CHD Mortality, and Total Mortality According to Elevated TSH Categories in Patients with Subclinical Hypothyroidism Data on 55,287 participants between 1972 and 2007 were supplied from 11 prospective cohorts in the United States, Europe, Australia, Brazil, and Japan Rodondi N et al. 2010 JAMA 304:1365-74

HTN risk in subclinical hypothyroidism Mean SBP and DBP by categories of TSH in men (n = 8,014) and women (n = 14,721), adjusted for age and smoking status SBP DBP Asvold, B. O. et al. J Clin Endocrinol Metab 2007;92:841-845

Correlation between weight and baseline TSH quartile Females Males Fox, Archives Internal Medicine, 2008

Subclinical hypothyroidism and CV risk Does LT4 replacement improve the CV risk factors?