Primary hypothyroidism

Polyglandular autoimmune syndrome type II (Addison s disease, primary hypothyroidism, primary hypogonadism, diabetes, and pernicious anemia)... 

There are three types of TH deficiency known to impact fetal development, including (Figure 108.1) isolated fetal hypothyroidism (congenital hypothyroidism CH), combined maternal and fetal hypothyroidism (endemic cretinism EC), and isolated maternal hypothyroidism (primary maternal hypothyroidism). According to the review of CH (American Academy of Pediatrics, 2006), TH deficiency originates from birth and is mainly due to the failure of... 

Disorders of lipoprotein metabolism involve perturbations which cause elevation of triglycerides and/or cholesterol, reduction of HDL-C, or alteration of properties of lipoproteins, such as their size or composition. These perturbations can be genetic (primary) or occur as a result of other diseases, conditions, or drugs (secondary). Some of the most important secondary disorders include hypothyroidism, diabetes mellitus, renal disease, and alcohol use. Hypothyroidism causes elevated LDL-C levels due primarily to downregulation of the LDL receptor. Insulin-resistance and type 2 diabetes mellitus result in impaired capacity to catabolize chylomicrons and VLDL, as well as excess hepatic triglyceride and VLDL production. Chronic kidney disease, including but not limited to end-stage... 

Once a euthyroid state is achieved, tlie primary health care provider may add a thyroid hormone to tlie therapeutic regimen to prevent or treat hypothyroidism, which may develop slowly during long-term antithyroid drug therapy or after administration of 131I. 

Inherited defects in lipoprotein metabofism lead to the primary condition of either hypo- or hyperlipoproteinemia (Table 26-1). In addition, diseases such as diabetes mellitus, hypothyroidism, kidney disease (nephrotic syndrome), and atherosclerosis are associated with secondary abnormal hpoprotein patterns that are very similar to one or another of the primary inherited conditions. Virtually all of the primary conditions are due to a defect at a stage in hpoprotein formation, transport, or destruction (see Figures 25—, 26-5, and 26-6). Not all of the abnormafities are harmful. 

Inherited defects in hpoprotein metabofism lead to a primary condition of hypo- or hyperfipoproteinemia. Conditions such as diabetes meUitus, hypothyroidism, kidney disease, and atherosclerosis exhibit secondary abnormal hpoprotein patterns that resemble certain primary conditions. 

Prolactin is an essential hormone for normal production of breast milk following childbirth. It also plays a pivotal role in a variety of reproductive functions. Prolactin is regulated primarily by the hypothalamus-pituitary axis and secreted solely by the lactotroph cells of the anterior pituitary gland. Under normal conditions, secretion of prolactin is predominantly under inhibitory control by dopamine and acts on the D2 receptors located on the lactotroph cells. Increase of hypothalamic thyrotropin-releasing hormone (TRH) in primary hypothyroidism can stimulate the release of prolactin. 

Primary hypothyroidism Adrenal insufficiency Reduced Prolactin Elimination... 

The vast majority of hypothyroid patients have thyroid gland failure (primary hypothyroidism). The causes include chronic autoimmune thyroiditis (Hashimoto s disease), iatrogenic hypothyroidism, iodine deficiency, enzyme defects, thyroid hypoplasia, and goitrogens. 

A rise in the TSH level is the first evidence of primary hypothyroidism. Many patients have a free T4 level within the normal range (compensated hypothyroidism) and few, if any, symptoms of hypothyroidism. As the disease progresses, the free T4 concentration drops below the normal level. The T3 concentration is often maintained in the normal range despite a low T4. Antithyroid peroxidase antibodies and antithyroglobulin antibodies are likely to be elevated. The RAIU is not a useful test in the evaluation of hypothyroidism because it can be low, normal, or even elevated. 

Replacement therapy of hypothyroidism. Whether primary, i.e caused by thyroid disease, or secondary, i.e resulting from TSH deficiency, hypothyroidism is treated by oral administration of T4. Since too rapid activation of metabolism entails the hazard of cardiac overload (angina pectoris, myocardial infarction), therapy is usually started with low doses and gradually increased. The final maintenance dose required to restore a euthyroid state depends on individual needs (approx. 

Increased = Decreased N = Normal X = Contraindicated Pregnancy Primary hypothyroidism Secondary hypothyroidism Hyperthyroidism... 

Dosage adjustment The levothyroxine dose generally is adjusted in 12.5 to 25 meg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized. 

The cornerstone of treatment in primary hyperlipidemia is diet restriction and weight reduction. Limit or eliminate alcohol intake. Use drug therapy in conjunction with diet, and after maximal efforts to control serum lipids by diet alone prove unsatisfactory, when tolerance to or compliance with diet is poor or when hyperlipidemia is severe and risk of complications is high. Treat contributory diseases such as hypothyroidism or diabetes mellitus. 

Thyrotropin-releasing hormone, or protirelin, consists of three amino acids. TRH (Relefact TRH) is used for tests to distinguish primary from secondary hypothyroidism (see Chapter 65). 

Secondary hypothyroidism, or pituitary hypothyroidism, is the consequence of impaired thyroid-stimulating hormone (TSH) secretion and is less common than primary hypothyroidism. It may result from any of the causes of hypopituitarism (e.g., pituitary tumor, postpartum pituitary necrosis, trauma). Patients with secondary hypothyroidism exhibit undetectable or inappropriately low serum TSH concentrations. In secondary hypothyroidism, a normal thyroid gland lacks the normal level of TSH stimulation necessary to synthesize and secrete thyroid hormones. Such patients usually also have impaired secretion of TSH in response to exogenous thyrotropin-releasing hormone (TRH) administration. 

Juvenile or adult patients with primary hypothyroidism (as indicated by low serum free T4 and high serum TSH concentrations) are usually treated with thyroxine with the aim of relieving symptoms and reducing the serum TSH concentration into the normal reference range. If the primary hypothyroidism is the result of iodine deficiency, then gradually increasing dietary iodine supplementation may also be instituted in addition to the thyroxine replacement therapy. Iodine supplementation alone may lead to the development of acute hyperthyroidism. 

Hypothyroidism, a condition in which the circulating concentrations of thyroid hormones are too low, is the most prevalent thyroid disease. Primary hypothyroidism, the commonest form, is an autoimmune disease (Hashimoto s thyroiditis) often associated with goitre. Like other autoimmune diseases, it is more prevalent in women (4 per 1000) than in men (1 per 1000). Other causes include thyroidectomy, radioac tive ablation and, in some countries, iodine deficiency. Hypothyroidism can also be caused by several drugs, including lithium, interleukin-2 and interferon. Secondary hypothyroidism is a disease caused by decreased secretion of TSH by the pituitary. 

In 50 women taking levothyroxine either for primary thyroid failure or for hypothyroidism secondary to radioiodine treatment for hyperthyroidism, there was no difference between the two groups in terms of bone density at the hip or spine and no difference from the reference population (31). In addition, there was no correlation between bone density and circulating thyroid hormone concentrations or duration of levothyroxine replacement. These findings are reassuring, although large studies of fracture risk are required, in view of previous evidence of an adverse effect of levothyroxine on bone mineral density, especially in post-menopausal women (32). 

Exley A, O Malley BP. Depression in primary hypothyroidism masquerading as inadequate or excessive L-thyroxine consumption. Q J Med 1989 72(269) 867-70. 

El Kaissi S, Kotowicz MA, Berk M, Wall JR. Acute delirium in the setting of primary hypothyroidism the role of thyroid hormone replacement therapy. Thyroid 2005 15(9) 1099-101. 

Shakir KM, Chute JP, Aprill BS, Lazarus AA. Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism. South Med J 1997 90(6) 637-9. 

Hattori N, Shimatsu A, Murabe H, Nishimura M, Nakamura H, Imura H. Clofibrate-induced myopathy in a patient with primary hypothyroidism. Jpn J Med 1990 29(5) 545-7. 

Patients with beta-thalassemia major have an increased risk of primary hypothyroidism. In 23 patients with beta-thalassemia amiodarone was associated with a high risk of overt hypothyroidism (33 versus 3% in controls) (43). This occurred at up to 3 months after starting amiodarone. The risk of subclinical hypothyroidism was similar in the two groups. In one case overt hypothyroidism resolved spontaneously after withdrawal, but the other patients were given thyroxine. After 21-47 months of treatment three patients developed thyrotoxicosis, with remission after withdrawal. There were no cases of hyperthyroidism in the controls. The authors proposed that patients with beta-thalassemia may be more susceptible to iodine-induced hypothyroidism, related to an underlying defect in iodine in the thyroid, perhaps associated with an effect of iron overload. 

A 63-year-old woman taking long-term lithium who developed subclinical hypothyroidism and primary hyperparathyroidism (641). 

The authors suggested that men with primary hypothyroidism may be particularly sensitive to neuroleptic drug-induced increases in prolactin concentrations. 

In a prospective, observational cohort study in a tertiary-care hospital, there were abnormal serum TSH concentrations in 26 of 42 patients) who took sunitinib for renal cell carcinoma or GIST. Persistent primary hypothyroidism, isolated TSH suppression, and transient mild rises in TSH were found in 36%, 10%, and 17% of patients respectively. There appears to be a correlation between the duration of use of sunitinib and suppressed TSH concentrations as well as a risk of hypothyroidism. Whether sunitinib induces destructive thyroiditis through follicular cell apoptosis has not been fully elucidated (1078,1079,1080). 

Lattanzi V, Scardapane R, Santoro G, Mongelli S, Glorgino R. 1979. [Chronobiological aspects of TSH secretion in control subjects and in subjects with primary hypothyroidism] In Italian. Boll Soc ItalBiol Sper 55 2358-2364. 

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