SLC26A4 mutation in Pendred syndrome with hypokalemia: A case report.

RATIONALE: Pendred syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss, inner ear malformations, goiter, and abnormal organification of iodide. It is caused by mutations in SLC26A4 gene, which encodes pendrin (a transporter of chloride, bicarbonate, and iodide). Pendred syndrome is a common cause of syndromic deafness, but the metabolic abnormalities it causes are often overlooked. Here, we report the case of a patient diagnosed with Pendred syndrome with hypokalemia. PATIENT CONCERNS: A 53-year-old deaf-mute woman was hospitalized due to severe limb asthenia. The emergency examination showed that her blood potassium level was 1.8 mmol/L. DIAGNOSES: Through the genetic test, we found a mutation of SLC26A4 gene in NM_000441: c.2027T>A, p.L676Q, as well as the SLC26A4 exon 5-6 deletion. These genetic variations pointed to Pendred syndrome (an autosomal recessive disorder that mainly affects the inner ear, thyroid, and kidney) which is a common cause of syndromic deafness. INTERVENTIONS: The patient was treated with potassium supplements and screened for the cause of hypokalemia. OUTCOMES: The patient was discharged after her potassium levels rose to the normal range. LESSONS: Patients with Pendred syndrome may also have certain metabolic abnormalities; thus, more attention should be paid to them during clinical diagnosis.

Recombinant human TSH and radioactive iodine therapy in the management of benign multinodular goiter.

Multinodular goiter (MNG) is a very common thyroid disorder determined by diverse goitrogenic factors, the most important one being iodine deficiency. The clinical presentation of a patient with MNG varies from a completely asymptomatic goiter to a life-threatening disease due to upper airway compression. Patients can develop underlying subclinical or overt hyperthyroidism due to autonomously hyperfunctioning nodules. In the absence of clinical, ultrasonographic, or cytological findings suggestive of malignancy, the best therapeutic approach for a patient with MNG will depend on the size and location of the goiter, the presence and severity of compressive symptoms, and the presence or absence of thyrotoxicosis. There is still no consensus regarding the treatment of atoxic MNGs. Hence, its optimal management remains controversial; possible therapies include levothyroxine (lT4), surgery, and radioactive iodine ((131)I). Suppressive treatment with lT4 is discouraged due to the development of sub-clinical or overt hyperthyroidism and to its low efficacy when compared with surgery or (131)I. Total thyroidectomy is effective; however, it is associated with the risk of surgical complications and is often refused by the patient. (131)I therapy is an alternative to thyroid surgery to reduce the size of benign MNGs. Based on the ability of recombinant human TSH (rhTSH) to more than double thyroid (131)I uptake, this compound has been evaluated as an adjuvant to (131)I in the treatment of MNG. Very small doses of rhTSH have been used in patients with MNG and few safety concerns have been observed, but the ideal dose, both effective and safe, is yet to be defined.

Refining calcium test for the diagnosis of medullary thyroid cancer: cutoffs, procedures, and safety.

CONTEXT: Calcitonin (CT) measurement is crucial to the early diagnosis and the follow-up of medullary thyroid cancer (MTC). If the evaluation of stimulated CT levels is required, a provocative test can be performed, being the high-dose Ca test recently reintroduced in clinical practice. OBJECTIVE: Our objective was to identify gender-specific thresholds for MTC diagnosis in a large series of patients who underwent the Ca test. PATIENTS AND METHODS: A total of 91 patients (49 females and 42 males) underwent the Ca test (calcium gluconate, 25 mg/kg) before thyroidectomy and both basal CT (bCT) and stimulated CT (sCT) were compared with histological results by receiver operating characteristic plot analyses. To evaluate possible side effects of Ca administration, cardiac function has been extensively studied. RESULTS: bCT levels were found to harbor the same accuracy as sCT in the preoperative diagnosis of MTC. The best Ca thresholds for the identification of MTC were >26 and >68 for bCT and >79 and >544 pg/mL for sCT in females and males, respectively. The high tolerability and safety of the Ca test was demonstrated and advice offered to be followed before and during the test. CONCLUSIONS: Gender-specific bCT and sCT cutoffs for the identification of C-cell hyperplasia and/or MTC have been defined. The bCT and sCT were found to have a similar accuracy, indicating that serum CT assays with improved functional sensitivity may likely decrease the relevance of the stimulation test in several conditions. Finally, systematic cardiac monitoring confirms the safety of the Ca test.

Concomitant hyperthyroidism in patients with thyroid carcinoma and the effects of iodine supplementation in an iodine-deficient area.

Objectives of this study were to investigate the occurrence and aggressiveness of differentiated thyroid carcinoma (DTC) in patients with hyperthyroidism and to explore the influence of the changes in dietary iodine intake on the association of hyperthyroidism and DTC. Clinical records of 1,800 patients with DTC were reviewed. The characteristics of DTC cases with and without thyrotoxicosis and their thyroid tumors were comparatively assessed.In the current series, 76 patients (4.2%) presented with hyperthyroidism before thyroid surgery. The most common type of goiter among 76 patients was toxic multinodular goiter. Presence of lymph node metastasis and recurrence was only observed in patients with toxic diffuse goiter. When DTC cases with and without thyrotoxicosis were compared irrespective of the type of goiter, aggressiveness of thyroid carcinoma was not higher in the thyrotoxic group. Hyperthyroidism and thyroid carcinoma coexisted in 3.3% and 4.7% in cases diagnosed before and after national iodine supplementation program, respectively (P = 0.04). Clinical course of the disease was not different in the diagnosis of these cases. As a result of no significant difference in complete remission ratio, we conclude that there is no need for a different DTC treatment protocol in cases with coexisting hyperthyroidism.

[65-year old female patient with persistent hypercalcemia]. / 65-jährige Patientin mit persistierender Hyperkalzämie.

A 65-year old patient presented with newly diagnosed hypercalcemia and elevated parathyroid hormone levels. Exploration of parathyroid glands was performed under the diagnosis of primary hyperparathyroidism and was combined with thyreoidectomy due to concomittant multinodular goiter. However, no parathyroid adenoma was identified despite careful exploration. Therefore, the operation was terminated and an ectopic adenoma was suspected. A (99m)Tc-sestamibi scintigraphy with SPECT, neck ultrasound, neck CT scan with contrast media and selective venous sampling were performed for further localization of the adenoma. A single adenoma localized in the submandibular area of the left jaw was suspected and confirmed during surgical reexploration. Postoperatively, parathyroid hormone levels were below detection level and the patient required short-term calcium supplementation for symptomatic hypocalcemia.

Radioiodine treatment of non-toxic multinodular goitre: effects of combination with lithium.

PURPOSE: This study aimed to evaluate the effects of radioiodine ((131)I), alone or in combination with lithium, on thyroid volume and the prevention of radioiodine-induced thyrotoxicosis. This is the first clinical trial including only patients with multinodular goitre, normal TSH values and negative anti-thyroid auto-antibodies at baseline. METHODS: Eighty consecutive patients were randomised to receive (131)I plus lithium (group I+L) or (131)I alone (group I). Thyroid ultrasonography and biochemical analyses were performed at baseline and at 1, 3, 6, 12 and 24 months after treatment. RESULTS: At 1-4 weeks after treatment, (131)I-induced hyperthyroidism was observed in 58.8% of patients and was prevented by lithium administration. A low incidence of hypothyroidism (19%) was recorded at 24 months, whereas up to 44% of patients developed anti-thyroid antibodies. A significant reduction in thyroid volume was observed after (131)I, with a mean decrease of 47.2% (median 48.2%) at 24 months, without differences between the groups. Moreover, it was shown that the decrease in thyroid volume after (131)I was also due to the significant shrinkage of thyroid nodules. CONCLUSION: This demonstrates that adjunctive lithium is able to reduce radioiodine-induced hyperthyroidism. Therefore, such treatment appears to be safe in older patients and those with underlying cardiovascular disease. In the present large series, (131)I therapy was demonstrated to be highly effective in reducing thyroid and nodular volume even in patients treated with low (131)I doses (2.5 MBq/ml of thyroid tissue), further supporting the view that radioiodine therapy represents a real alternative to surgery.

Uses for recombinant human TSH in patients with thyroid cancer and nodular goiter.

Recombinant human TSH (rhTSH) has revolutionized the care of patients with differentiated thyroid cancer. Since its approval for clinical use in 2001 in Europe (1998 in the USA), rhTSH has greatly enhanced the surveillance of these patients by allowing the avoidance of hypothyroidism for TSH stimulation. Previously, a hypothyroid state was required for TSH stimulated diagnostic whole-body radio-iodine scans (DxWBS) and thyroglobulin (Tg) levels. Patients generally prefer rhTSH as a mechanism for TSH stimulation because symptoms of hypothyroidism can be completely avoided. Currently, rhTSH is only approved for diagnostic monitoring of differentiated thyroid cancer patients. There are many other potential uses for rhTSH, including facilitation of treatment of patients with thyroid cancer and nodular goiter. The diagnostic and therapeutic role of rhTSH in patients with differentiated thyroid cancer and nodular goiter will be discussed in this review.

Management of the nontoxic multinodular goitre: a European questionnaire study.

BACKGROUND AND OBJECTIVE: The optimum management strategy for the patient with a multinodular nontoxic goitre is still a matter of debate. Our aim was to assess the attitudes towards management of such patients throughout Europe by means of a questionnaire. DESIGN: The questionnaire was circulated to all clinician members of the European Thyroid Association (ETA). A case report was followed by diagnostic investigations and choice of therapy in the index case (a 42-year-old woman with an irregular nontender bilaterally enlarged thyroid of 50-80 g and no clinical suspicion of malignancy). Eleven variations of the basic case report were proposed in order to evaluate the impact on management of each alteration. SUBJECTS AND METHODS: One hundred and sixty-seven members replied to the letter, and 120 individuals from 22 countries completed the questionnaire (corresponding to approximately two-thirds of the clinical members of the ETA). RESULTS: Based on the index case, serum TSH was the routine choice of 100%, and serum free T4/T4-index was included by 74%. Serum TPO autoantibodies, Tg autoantibodies and calcitonin were measured by 65%, 49% and 32%, respectively. The median number of blood tests used was four (range 1-11). Considerable intercountry variations were seen in the preferred imaging methods. Ninety-one percent of the clinicians would use at least one imaging modality. Ultrasound (US) was used by 84%, thyroid scintigraphy by 76%, and both methods by 69%. US had first priority (53% vs. 19% for scintigraphy). If scintigraphy was performed, fine-needle aspiration cytology was routinely used by 17% (inhomogeneous uptake) and 95% (dominant 'cold' area), and 63% used US-guidance. L-T4 treatment was supported by 52% of the clinicians, iodine supplementation by 4%, radioiodine by 6% and surgery by 10%. In the case of a suppressed serum TSH, radioiodine treatment was preferred by 44%, while surgery was the favoured recommendation in four clinical variations with a large goitre or suspicion of malignancy. Marked differences between the countries were suggested by L-T4 therapy being the dominant treatment in Italy, France and Germany in contrast to the prevailing use of radioiodine in Denmark and a wait and see policy in the UK. CONCLUSIONS: Fundamental differences between European countries exist as regards diagnosis and treatment of the multinodular nontoxic goitre suggesting difficulties in reaching a consensus.

[Thyrotoxic crisis after exposure to iodine. A case with fatal outcome]. / Thyreotoxische Krise nach Jodexposition. Ein Fall mit letalem Ausgang.

A 78-year-old woman is presented with a multinodular toxic goiter and euthyroidism under continuous low-dose treatment with antithyroid drugs. A period of hyperthyroidism had been documented 3 years previously. In the preoperative management, prior to resection of a benign ovarian tumour, an intravenous urogram was performed. Perchlorate was given for thyroid protection. One day after surgery the clinical signs of thyroid storm were observed. Immediately, high-dose antithyroid drug therapy was started. Nevertheless, the patient died of acute cardiovascular failure 3 days later. This case report focuses on the risk of thyroid storm following iodine excess in the presence of relevant functional thyroid autonomy without adequate thyroid protection.

[Neck tumors: struma]. / Halstumoren: struma.

Goiters are most commonly caused by increased, usually nodular growth of thyroid tissue ('simple' goiter), stimulation of thyroid growth by autoantibodies (Grave's disease) or thyroiditis. Rarer causes of goiter are malignant thyroid tumors and hereditary disturbances of thyroid hormone synthesis goiter: due to iodine deficiency should be found no longer in Switzerland because of the adequate iodine supplementation in this country. Differentiating the various types of goiters is usually possible on the basis of clinical signs and a few laboratory tests (e.g. measurement of thyroid antibodies). 'Simple' goiter is usually treated surgically. Hyperthyroid Grave's goiter is primarily treated with thyrostatic drugs, if it recurs; radioiodine of surgery are also used. Subacute thyroiditis causing goiter is treated symptomatically with analgesics anti-inflammatory drugs, while patients with chronic thyroiditis are given thyroid hormones when hypothyroidism occurs. Malignant tumors of the thyroid are treated surgically; in some cases additional therapy with radioiodine is indicated.

The autonomously functioning thyroid nodule: Goetsch's disease.

The AFTN was established as a clinical entity by the 1918 report of Goetsch, correlating cellular mitochondrial content with nodular function, and showing the inverse correlation between AFTN function and extranodular tissue function. Degeneration, common in AFTNs, can preclude development of hyperthyroidism, eliminate hyperthyroidism, or even induce transient spontaneously resolving hyperthyroidism. AFTNs are nearly always benign. Most reports of malignant AFTNs are inadequately documented. Whether AFTNs are toxic can be determined by clinical evaluation, with laboratory confirmation using principally serum T3 assays and TRH testing. Whether warm nodules are AFTNs may be determined by suppression imaging. Nontoxic AFTNs are usually observed. For older patients with borderline high serum T3 levels, blunted responses to TRH, or subnormal responses on supersensitive TSH assays, prophylactic therapy may be prudent. Toxic AFTNs may be treated surgically (patients younger than 40) or with radioactive iodine (older patients). High dose radioactive iodine therapy is preferred because it more consistently ablates AFTN function.

Diagnosis and management of large toxic multinodular goiters.

Toxic multinodular goiters, estimated weight 100 g or more, occurred in 35 patients between 1961 and 1984. All but two were older than 50; 32 were females. Twenty had goiters of 100-130 g; four of 140-200 g; and 11 were massive. Radioiodine uptakes were 30% or less for 22. Seven of 17 with both T4 and T3 data had T4 toxicosis. Thirty-two patients received radioiodine therapy, delivering 200 microCi per gram when possible. Doses were 25-30 mCi for 17 patients; 50-100 mCi for 12 patients, and 150-200 mCi for three patients. Hyperthyroidism was eliminated with one dose in 25 patients (78%); five patients required two doses. Twenty-two patients were euthyroid after radioiodine; 25 of 28 had persistent goiters. Two patients were treated successfully surgically. One refused surgery and radioiodine, and has been maintained on antithyroid drugs for 10 yr. Two patients died within a few months of an unsuccessful initial dose of radioiodine. Large dose radioiodine therapy is simple, safe, and effective for most patients with large toxic multinodular goiters.

Thyroid disease: a guide for the head and neck surgeon.

Head and neck surgeons are involved in the diagnosis and therapy of thyroid disease with increasing frequency. The surgical techniques utilized for the management of thyroid disease are well known by most head and neck surgeons and will not be discussed in this paper. It is the head and neck surgeons' knowledge of the physiology, medical disorders, and the proper evaluation of the patient with thyroid disease that is most open to criticism. This paper reviews thyroid physiology, basic tests used to assess thyroid function in health and disease, thyroiditis, thyroid carcinomas, and nodules of the thyroid gland. The signs, symptoms, laboratory findings, and the methods of medical and surgical therapy are discussed for each of these disorders. The supplement is not intended to provide expertise, but will provide a general and basic knowledge of thyroid disease.