Secondary hypothyroidism occurs after pituitary gland malfunction results in reduced release of thyroid stimulating hormone (TSH). TSH, in turn, activates the thyroid gland, leading to a release of thyroxine or T4 and triiodothyronine or T3 hormones. Thus clinical presentation will be dependent on dysfunctional pituitary and on the hypothyroid state of the patient. Secondary hypothyroidism can be acquired or congenital. The latter is linked to more severe dynamics, retardation of skeletal growth, and disturbed mental development [1].

Pituitary dysfunction can occur due to a tumor that compresses the gland and interferes with its functioning. Craniopharyngiomas, brain tumors, and hematologic malignancies can present the etiologic factor in children [2]. Chemotherapy administration in leukemic children can also cause damage to the gland [3]. Adults generally present with macroadenoma of the pituitary or have had previous exposure to iatrogenic factors such as radiation therapy or surgeries with a high risk of pituitary trauma [4]. Reduced secretion of hormones from the pituitary gland apart from TSH also contributes to clinical presentation. Failed release may lead to amenorrhea, infertility, weight loss, hypoglycemia, and diabetes insipidus [5].

Clinical presentation of a hypothyroid state differs by some factors. Such factors are the age of onset, duration of hypothyroidism, the cause of the disease, and extent of additional contribution to the presentation by the pituitary gland. Generally, hypothyroidism is associated with slower basal metabolic rate, patients may gain weight by retention of salt, water, and an increase in body fat. About 10% increase in body weight is usually observable. Fat tissue is affected by disrupted lipolysis and biosynthesis of fatty acids. Other manifestations include fatigue, headaches, periorbital edema, adynamia, constipation, dryness of skin, intolerance to cold, and cardiovascular signs such as bradycardia [5].

• Fatigue

  Adrenal fatigue can be mild to moderate to severe. When severe, it's usually referred to as adrenal exhaustion (v. fatigue). [patient.info]

  Adrenal Fatigue and Hypothyroidism The following table outlines the key differences in the signs and symptoms between Adrenal Fatigue and hypothyroidism symptoms. [drlam.com]

  You mentioned your adrenals, but adrenal fatigue is hard to diagnose with just one test. Weight gain, salt craving and fatigue are symptoms. Also you might want to check out your estrogen/progesterone ratio (estrogen dominance). [medhelp.org]

• Weight Gain

  Thyroid Disorders Community 26k Members I went to the doctor over a year ago with complaints of weight gain, (40 lbs at that time), dry skin, and exhaustion. I was having a hard time functioning in general. [medhelp.org]

  Alopecia, weight gain, mental dullness, fatigue, cold intolerance, infertility and neurological deficits are seen. In food animals the syndrome is classical neonatal colloid goiter. [medical-dictionary.thefreedictionary.com]

  The signs are associated with decreased metabolism, such as personality changes, forgetfulness, and weight gain, says Healthline. Other symptoms include sensitivity to cold, constipation, and tingling or burning sensations in the hands and feet. [newsmax.com]

  If the thyroid is not functioning properly, health problems can ensue such as fatigue, weight gain, and a decreased ability to tolerate cold. [progressivehealth.com]

• Myxedema

  PubMed Search : hypothyroidism adult myxedema Page views in 2018: 1,806 Page views in 2019 to date: 255 Cite this page: Hypothyroidism (adult) and myxedema. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidhypo.html. [pathologyoutlines.com]

  Myxedema coma can result in death. Complications: Myxedema coma, the most severe form of hypothyroidism, is rare. It may be precipitated by an infection, illness, exposure to cold, or certain medications. [endocrinesurgery.ucla.edu]

  More severe manifestations may include myxedematous heart disease and myxedema coma, which may be fatal if left untreated. [amboss.com]

  Myxedema Hypothyroidism, when left unchecked and untreated can lead to a very serious condition known as Myxedema. [progressivehealth.com]

• Weakness

  Children who have secondary hypothyroidism will have the following symptoms: Secondary Hypothyroidism symptoms Early Symptoms Late Symptoms weakness slow speech fatigue dry flaky skin cold intolerance thickening of the skin constipation puffy face, hands [dshs.state.tx.us]

  Symptoms: Early symptoms: Weakness Fatigue Cold intolerance Constipation Weight gain Depression Joint or muscle pain Brittle fingernails Coarseness, thinning of hair Late symptoms: Slow speech Dry, flaky skin Thickening of the skin Puffy face, hands, [endocrinesurgery.ucla.edu]

  However, it is also important not to under-treat these elderly patients for fear of adverse effects because they are more susceptible to confusion, memory loss, muscle weakness and falls if their dosage is not adequate enough. [physio-pedia.com]

• Hypothermia

  Thyroid 2012;22:1200 ) Rarely presents with myxedema pseudovolvulus ( J Surg Case Rep 2016 Apr 22;2016(4) ) or severe hyponatremia ( Eur J Endocrinol 2017;176:R15 ) Myxedema coma is characterized by unconsciousness, respiratory failure, bradycardia, hypothermia [pathologyoutlines.com]

  Its characteristics include coma with extreme hypothermia (temperature 24° to 32.2° C), areflexia, seizures, and respiratory depression with carbon dioxide retention. Severe hypothermia may be missed unless low-reading thermometers are used. [merckmanuals.com]

  Mental status changes including lethargy, cognitive dysfunction, and even psychosis, and hypothermia are the hallmark features of myxedema coma. 33 Hyponatremia, hypoventilation, and bradycardia can also occur. [aafp.org]

  Serious complications may occur if hypothyroidism left untreated: Cardiovascular heart disease, due to high levels of cholesterol and triglyceride Myxoedema coma (hypothyroid coma), characterised by hypothermia, reduced level of consciousness and seizures [dermnetnz.org]

  Hypothermia Features of hypothyroidism. Precipitating factors include sedative drugs and anything that impairs the respiratory system - eg, pneumonia, cardiac failure and myocardial infarction [ 25 ]. [patient.info]

• Hoarseness

  It is diagnosed by clinical features such as a typical facial appearance, hoarse slow speech, and dry skin and by low levels of thyroid hormones. Management includes treatment of the cause and administration of thyroxine. [msdmanuals.com]

  The voice is sometimes affected by hoarseness or slow speech. Facial puffiness may occur. Urgent: Dr. [newsmax.com]

  […] symptoms Early Symptoms Late Symptoms weakness slow speech fatigue dry flaky skin cold intolerance thickening of the skin constipation puffy face, hands and feet weight gain decreased taste and smell depression thinning of eyebrows joint or muscle pain hoarseness [dshs.state.tx.us]

  Postpartum Umbilical hernia Prolonged newborn jaundice Hypotonia Decreased activity, poor feeding, and adipsia Hoarse cry, macroglossia Cretinism ; : impaired development ; of the brain and skeleton, resulting in skeletal abnormalities ; and intellectual [amboss.com]

  Question One of my patient is a 54 y.o., poor, medically uninsured female suffering evidently from hypothyroidism: since 2 years, she has become progressively fatter, weaker, has menorrhagia, hoarseness of her voice, decrease hearing, and feels depressed [endotext.org]

• Constipation

  A high-fiber, low-calorie diet and moderate activity will help relieve constipation and promote weight loss if weight was gained during the time when thyroid activity was low. [endocrinesurgery.ucla.edu]

  Other manifestations include fatigue, headaches, periorbital edema, adynamia, constipation, dryness of skin, intolerance to cold, and cardiovascular signs such as bradycardia. [symptoma.com]

  Other symptoms include sensitivity to cold, constipation, and tingling or burning sensations in the hands and feet. The voice is sometimes affected by hoarseness or slow speech. Facial puffiness may occur. Urgent: Dr. [newsmax.com]

• Heart Disease

  Drug causes: Lack of iodine in diet Gross excess iodine in diet Enzyme defects in the thyroid (dyshormonogenesis) Over treatment with antithyroid drugs in thyrotoxicosis Lithium treatment in mental disease Amiodarone treatment in heart disease Thalidomide [endocrinesurgeon.co.uk]

  More severe manifestations may include myxedematous heart disease and myxedema coma, which may be fatal if left untreated. [amboss.com]

  Symptoms and signs of myxedema coma include: Unresponsiveness Decreased breathing Low blood pressure Low blood sugar Below-normal temperature Other complications include: Heart disease Infertility Miscarriage in pregnant women Adrenal crisis, if thyroid [endocrinesurgery.ucla.edu]

  Radioactive iodine (used to treat hyperthyroidism ) Amiodarone, an iodinated drug used in heart disease, which can induce both hyperthyroidism and hypothyroidism Lithium, often used for mental illness and eating disorders. [dermnetnz.org]

• Jaundice

  Within the first month after birth, the patient manifested feeding difficulties, lethargy, persistent jaundice, umbilical hernia, and large anterior and open posterior fontanels. [ncbi.nlm.nih.gov]

  Mainz, Mainz, Germany; b University of Alberta Hospital, Edmonton, Alberta, Canada; c Pediatric Endocrinology, Walter Mackenzie Health Sciences Centre, Edmonton, Alberta, Canada Background: A 6-week-old male was admitted for investigation of prolonged jaundice [abstracts.eurospe.org]

  Common clinical features and signs include decreased activity and increased sleep, feeding difficulty and constipation, prolonged jaundice, myxedematous facies, large fontanels (especially posterior), macroglossia, a distended abdomen with umbilical hernia [orpha.net]

  Neonatal hypothyroidism, called cretinism, is associated with mental retardation, jaundice (yellowing of skin), poor feeding, breathing difficulties, and growth problems. [medbroadcast.com]

• Sparse Hair

  […] outer 1/3 Hair Thin, sparse on extremities Coarse and sparse Hair loss Sometimes Common Nails Thin, brittle Normal to thick Peri-orbital Tissue Sunken Puffy Skin Thin Normal Skin tone Dry Oily or moist Internal feeling Ligaments Flexibility Good Poor [drlam.com]

  This can develop into myxoedema: Expressionless dull face with peri-orbital puffiness, swollen tongue, sparse hair. Pale, cool skin with rough, doughy texture. Enlarged heart. Megacolon/intestinal obstruction. Cerebellar ataxia. Psychosis. [patient.info]

• Alopecia

  Alopecia, weight gain, mental dullness, fatigue, cold intolerance, infertility and neurological deficits are seen. In food animals the syndrome is classical neonatal colloid goiter. [medical-dictionary.thefreedictionary.com]

• Large Anterior Fontanels

  […] with swollen limbs and genitalia Large anterior fontanelle Cold and mottled skin especially on the extremities Flattened or broadened nose associated with nasal obstruction Macroglossia (enlarged tongue) Goitre Umbilical hernia Cardiac abnormalities: [dermnetnz.org]

• Apathy

  As in primary hypothyroidism, the symptoms of central hypothyroidism include fatigue, apathy, weight gain, dry skin, constipation and cold intolerance. [pituitarydisorder.net]

  […] teeth, drooping eyelids, swollen tongue extreme joint and bone pain, muscle weakness, hearing loss, intermittent vision loss, vertigo, cellulitis, plantar fascitis, insomnia, red/pink/white stretch marks across stomach and breasts couldn't sleep enough apathy [healthboards.com]

  First, it helps to rebuild activity tolerance, increase muscle strength, and reduce apathy secondary to the decreased metabolism caused by the disorder. [physio-pedia.com]

• Hyperactivity

  Hypo-reactive Medical condition History of Infections Common Occasional Chronic Fatigue Yes Yes Orthostatic Hypotension Frequent No Blood Sugar Levels Tendency toward hypoglycemia Normal to hyperglycemia Heart Palpitation Frequent No GI function Irritable or hyperactive [drlam.com]

  How About If You Have a Hyperactive Thyroid? Thyroxine or T4 is a hormone made by the thyroid gland carried throughout your body in your bloodstream. Many of your cells and tissues depend on thyroxine to work properly. [mercola.com]

  Even with treatment, some children with severe hypothyroidism may have attention problems and hyperactivity. [pennstatehershey.adam.com]

• Sexual Dysfunction

  Female sexual dysfunction [ 9 ]. Hypercholesterolaemia. This can develop into myxoedema: Expressionless dull face with peri-orbital puffiness, swollen tongue, sparse hair. Pale, cool skin with rough, doughy texture. Enlarged heart. [patient.info]

Secondary hypothyroidism diagnosis is based on clinical presentation and evaluation of thyroid stimulating hormone (TSH), T3, and T4 hormone levels in the serum. TSH measurement exhibiting high levels of TSH implies primary hypothyroidism disregarding the etiological factor or severity of the disease and excludes secondary hypothyroidism as a possible cause [6]. The acceptable range of TSH in a healthy human is 0.4 mIU/L to 4.0 mIU/L and may vary between age groups, nationalities, and races. For example, blacks tend to have lower levels of TSH than other races. This finding established a ground for the introduction of TSH reference range regulations based on variables of age and ethnicity [7].

Laboratory findings indicative of secondary hypothyroidism is subnormal or decreased TSH due to this hormone's delayed or disturbed secretion into the bloodstream. Because TSH is secreted improperly, FT4 levels (standing for free thyroxine or free T4) will be low as well due to hypostimulation of the thyroid gland [8].

By definition, secondary hypothyroidism occurs in cases of pituitary impairment. That is why imaging studies such as MRI scan of the head are essential diagnostic tools for discovering the cause of the disease [8].

• Pericardial Effusion

  effusion; pericardial effusions develop slowly and only rarely cause hemodynamic distress) Other manifestations: Pleural or abdominal effusions (pleural effusions develop slowly and only rarely cause respiratory or hemodynamic distress), hoarse voice [merckmanuals.com]

  Patients with severe hypothyroidism may present with pericardial effusion, pleural effusion, megacolon, hemodynamic instability, and coma. The clinical presentation is often confused with septic shock. [aafp.org]

  effusion Heart dilation ** Poor Peripheral Circulation may demonstrate as skin pallor, intolerance to cold, cool skin, or hypertension. [physio-pedia.com]

Intervention: Three different treatment regimes (5 weeks each) were compared: "CON-T4", empirically chosen, current dose of T4 (1 ± 0.05 μg/kg body weight (bw); "OPT-T4", optimized T4 treatment (1.6 μg/kg bw T4); "T3T4", combination of triiodothyronine [clinicaltrials.gov]

Awareness of risk may allow early diagnosis and treatment. [endocrinesurgery.ucla.edu]

Managing Treatment Nonadherence For patients with suboptimal adherence to daily levothyroxine treatment, use of observed therapy and reducing the frequency of treatment to twice weekly or weekly may be considered. [endocrineweb.com]

A persistently "hypothyroid state" (total T4: 23 +/- 15 nmol/l, free T4: 6.1 +/- 3.2 pmol/l, total T3: 0.28 +/- 0.22 nmol/l, S.D.) is associated with a very poor prognosis. [ncbi.nlm.nih.gov]

Support Groups: Expectations (prognosis): With early treatment, return to the normal state is usual. However, relapses will occur if the medication is not continued. Myxedema coma can result in death. [endocrinesurgery.ucla.edu]

Subclinical Hypothyroidism Is Associated With Adverse Prognosis in Heart Failure Patients. Can J Cardiol. 2018 Jan. 34 (1):80-7. [Medline]. Zamfirescu I, Carlson HE. Absorption of levothyroxine when coadministered with various calcium formulations. [emedicine.medscape.com]

Craniopharyngiomas, brain tumors, and hematologic malignancies can present the etiologic factor in children. Chemotherapy administration in leukemic children can also cause damage to the gland. [symptoma.com]

etiology ( Thyroid 2012;22:1200 ) Interference with thyroid hormone synthesis (idiopathic, genetic [ J Med Genet 2005;42:379 ], drugs [lithium, iodide, methimazole, PTU]) Supraphysiologic Iodine exposure, especially in those with preexisting thyroid [pathologyoutlines.com]

The etiology of acquired hypothyroidism is commonly autoimmune ( Hashimoto's thyroiditis ) or iatrogenic. The pathophysiology in hypothyroidism is characterized mainly by a reduction of the basal metabolic rate as well as generalized myxedema. [amboss.com]

Summary Epidemiology Prevalence is unknown. [orpha.net]

Epidemiology References: [1] [2] [3] Epidemiological data refers to the US, unless otherwise specified. [amboss.com]

Large epidemiological studies generally suggest no association between thyroid function and depression in people without thyroid disease. [patient.info]

Epidemiology Prevalence: clinical primary hypothyroidism, 0.3%; subclinical disease, 4.3% ( Thyroid 2012;22:1200 ) Myxedema crisis / coma has a higher incidence among older females, affects about 220,000 people per year ( J Thyroid Res 2011;2011:493462 [pathologyoutlines.com]

The pathophysiology of this relationship has yet to be completely elucidated, but elevated levels of thyroxine in the aqueous humor and tear film and thyroxine receptors in the cornea likely play a role. [ncbi.nlm.nih.gov]

The pathophysiology in hypothyroidism is characterized mainly by a reduction of the basal metabolic rate as well as generalized myxedema. [amboss.com]

Epidemiology Prevalence: clinical primary hypothyroidism, 0.3%; subclinical disease, 4.3% ( Thyroid 2012;22:1200 ) Myxedema crisis / coma has a higher incidence among older females, affects about 220,000 people per year ( J Thyroid Res 2011;2011:493462 ) Pathophysiology [pathologyoutlines.com]

To understand a test’s scientific basis and what it can tell us, a quick review of the thyroid gland’s pathophysiology is in order. [clinicaladvisor.com]

Secondary hypothyroidism is preventable. True False 8. You are at increased risk of developing secondary hypothyroidism, if you received radiation to the pituitary gland or hypothalamus in the past. True False 9. [quest4health.com]

Prevention: This condition may not be preventable. Awareness of risk may allow early diagnosis and treatment. [endocrinesurgery.ucla.edu]

It would help to prevent symptoms of hypothyroidism in affected individuals. [abstracts.eurospe.org]

LeFevre ML; US Preventive Services Task Force. Screening for thyroid dysfunction: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162(9):641-650. PMID: 25798805 www.ncbi.nlm.nih.gov/pubmed/25798805. [pennstatehershey.adam.com]

1. Lania A, Persani L, Beck-Peccoz P. Central hypothyroidism. Pituitary. 2008;11:181–186.
2. Schmiegelow M, Feldt-Rasmussen U, Rasmussen AK, Poulsen HS, Müller J. A Population-based study of thyroid function after radiotherapy and chemotherapy for a childhood brain tumor. J Clin Endocr Metab. 2003;88:136–140.
3. Baronio F, Battisti L, Radetti G. Central hypothyroidism following chemotherapy for acute lymphoblastic leukemia. J Pediatr Endocrinol Metab. 2011;24:903–906.
4. Rose SR. Cranial irradiation and central hypothyroidism. Trends Endocr Metab. 2001;12:97–104.
5. Gupta V, Lee M. Central hypothyroidism. Indian J Endocrinol Metab. 2011;15(2):S99-S106.
6. Carter Y, Sippel RS, Chen H. Hypothyroidism After a Cancer Diagnosis: Etiology, Diagnosis, Complications, and Management. Oncologist. 2014;19(1):34-43.
7. Surks MI, Boucai L. Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab. 2010;95:496–502.
8. Kostoglou-Athanassiou I, Ntalles K. Hypothyroidism - new aspects of an old disease. Hippokratia. 2010;14(2):82-87.