Thyroid Stimulating Hormone Stability in Patients Prescribed Synthetic or Desiccated Thyroid Products: A Retrospective Study.

The purpose of this retrospective matched-cohort study was to evaluate the stability of thyroid stimulating hormone (TSH) in patients using synthetic compared with desiccated thyroid products. Patients using a thyroid product for the treatment of hypothyroidism were matched 1:1 on age, sex, race/ethnicity, and had a follow-up period of 3 years after the index date. The primary outcome was percent of in-range TSH values. Over 3 years, TSH values in both groups were in-range 79% of the time (P = 0.905). Our results showed no difference in longitudinal TSH stability between desiccated thyroid products and synthetic levothyroxine.

Patient Experiences and Perceptions Associated with the Use of Desiccated Thyroid Extract.

Background and objectives: It is unclear why many patients with hypothyroidism prefer the use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over levothyroxine (LT4) treatment, as recommended by clinical practice guidelines. We analyzed patient-reported information from patient online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. Materials and Methods: We conducted a mixed-methods study by evaluating the content of online posts from three popular hypothyroidism forums from patients currently taking DTE (n = 673). From these posts, we extracted descriptive information on patient demographics and clinical characteristics and qualitatively analyzed posts' content to explore patient perceptions on DTE and other therapies further. Results: Nearly half (46%) of the patients reported that a clinician initially drove their interest in trying DTE. Patients described many reasons for switching from a previous therapeutic approach to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of side effects (22%). The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). The most frequently described benefits associated with DTE use were an improvement in symptoms (56%) and a change in overall well-being (34%). One-fifth of patients described side effects related to the use of DTE. Qualitative analysis of posts' content supported these findings and raised additional issues around the need for individualizing therapy approaches for hypothyroidism (e.g., a sense of each patient has different needs), as well as difficulties obtaining DTE (e.g., issues with pharmacy availability). Conclusions: Lack of individualized treatment and a feeling of not been listened to were recurrent themes among DTE users. A subset of patients may prefer DTE to LT4 for many reasons, including perceived better effectiveness and improved overall well-being, despite the risks associated with DTE.

From hormone replacement therapy to regenerative scaffolds: A review of current and novel primary hypothyroidism therapeutics.

Primary hypothyroidism severely impacts the quality of life of patients through a decrease in the production of the thyroid hormones T3 and T4, leading to symptoms affecting cardiovascular, neurological, cognitive, and metabolic function. The incidence rate of primary hypothyroidism is expected to increase in the near future, partially due to increasing survival of patients that have undergone radiotherapy for head and neck cancer, which induces this disease in over half of those treated. The current standard of care encompasses thyroid hormone replacement therapy, traditionally in the form of synthetic T4. However, there is mounting evidence that this is unable to restore thyroid hormone signaling in all tissues due to often persistent symptoms. Additional complications are also present in the form of dosage difficulties, extensive drug interactions and poor patience compliance. The alternative therapeutic approach employed in the past is combination therapy, which consists of administration of both T3 and T4, either synthetic or in the form of desiccated thyroid extract. Here, issues are present regarding the lack of regulation concerning formulation and lack of data regarding safety and efficacy of these treatment methods. Tissue engineering and regenerative medicine have been applied in conjunction with each other to restore function of various tissues. Recently, these techniques have been adapted for thyroid tissue, primarily through the fabrication of regenerative scaffolds. Those currently under investigation are composed of either biopolymers or native decellularized extracellular matrix (dECM) in conjunction with either primary thyrocytes or stem cells which have undergone directed thyroid differentiation. Multiple of these scaffolds have successfully restored an athyroid phenotype in vivo. However, further work is needed until clinical translation can be achieved. This is proposed in the form of exploration and combination of materials used to fabricate these scaffolds, the addition of peptides which can aid restoration of tissue homeostasis and additional in vivo experimentation providing data on safety and efficacy of these implants.

Primary hypothyroidism presenting as multiple ovarian cysts in an adult woman: a case report.

A 21-year-old woman was referred because of abdominal pain. On physical examination, her abdomen was distended up to the umbilical region. Ultrasound and computer tomography of the abdomen revealed bilateral multiple ovarian cysts. Laboratory studies revealed increased liver function, total cholesterol and creatine phosphokinase. Further clinical investigations determined that the patient suffered from primary hypothyroidism due to autoimmune thyroiditis. The cysts resolved spontaneously after the simple replacement of a thyroid hormone. Some reports have been published of primary hypothyroidism presenting as ovarian cysts and precocious puberty in prepubertal girls. However, the case presented herein indicates that an ovarian tumor as a result of hypothyroidism may also occur in adult females. To avoid inadvertent surgery to remove an ovarian tumor, it is essential that a patient with multiple ovarian cysts and hypothyroidism be properly managed, as the simple replacement of a thyroid hormone could resolve the ovarian cysts.

Physician Choice of Hypothyroidism Therapy: Influence of Patient Characteristics.

BACKGROUND: Most endocrinologists encounter patients who are dissatisfied with their current hypothyroidism therapy and request combination therapy with either liothyronine (LT3) or thyroid extract. METHODS: A survey of American Thyroid Association members was conducted in 2017. Respondents were presented with 13 scenarios describing patients with hypothyroidism and were asked to choose among six therapeutic options. The index patient was satisfied taking levothyroxine (LT4) therapy. Twelve variations introduced parameters that potentially provide reasons for considering combination therapy (presence of symptoms, low serum triiodothyronine concentration, documentation of deiodinase polymorphisms). Therapeutic options included (i) continuing LT4, (ii) increasing LT4, (iii) adding LT3 to a reduced LT4 dose, (iv) adding LT3 to the current LT4 dose, (v) replacing LT4 with thyroid extract, and (vi) replacing LT4 with LT3. Repeated-measures logistic regression analysis was performed to examine both the prescribing of LT4 (options i and ii) versus all other therapies and the choice of continuing LT4 (option i) versus either increasing LT4 (option ii), adding LT3 (options iii and iv), or replacing LT4 with thyroid extract or LT3 (options v and vi). RESULTS: Of the 389 survey respondents, 363 physicians prescribed therapy for hypothyroidism. For the index patient, 98% of physicians continued current LT4 therapy. However, as the patient scenario incorporated other patient characteristics, physicians opted to increase LT4 dose or prescribe other therapies. The tendency to prescribe alternative therapies was powerfully increased by patient symptoms (odds ratio = 25.6 [confidence interval 9-73], p < 0.0001). Older age and the presence of a comorbidity reduced the likelihood that an alternative therapy was prescribed (p = 0.0002 and <0.0001, respectively). All other characteristics, except athyreotic status, patient sex, and body mass index, significantly increased the likelihood that alternative therapies would be prescribed in multivariate analyses (p < 0.0001). CONCLUSIONS: Even with the acknowledged limitations of survey methodology, this analysis appears to show a marked increase in the willingness of physicians to prescribe combination therapy in specific circumstances. If current prescribing patterns do incorporate the use of therapies other than LT4, there is a critical need for more research into the benefits and risks of these therapies.

The emergence of levothyroxine as a treatment for hypothyroidism.

OBJECTIVE: To describe the historical refinements, understanding of physiology and clinical outcomes observed with thyroid hormone replacement strategies. METHODS: A Medline search was initiated using the search terms, levothyroxine, thyroid hormone history, levothyroxine mono therapy, thyroid hormone replacement, combination LT4 therapy, levothyroxine Bioequivalence. Pertinent articles of interest were identified by title and where available abstract for further review. Additional references were identified in the course of review of the literature identified. RESULTS: Physicians have intervened in cases of thyroid dysfunction for more than two millennia. Ingestion of animal thyroid derived preparations has been long described but only scientifically documented for the last 130 years. Refinements in hormone preparation, pharmaceutical production and regulation continue to this day. The literature provides documentation of physiologic, pathologic and clinical outcomes which have been reported and continuously updated. Recommendations for effective and safe use of these hormones for reversal of patho-physiology associated with hypothyroidism and the relief of symptoms of hypothyroidism has documented a progressive refinement in our understanding of thyroid hormone use. Studies of thyroid hormone metabolism, action and pharmacokinetics have allowed evermore focused recommendations for use in clinical practice. Levothyroxine mono-therapy has emerged as the therapy of choice of all recent major guidelines. CONCLUSIONS: The evolution of thyroid hormone therapies has been significant over an extended period of time. Thyroid hormone replacement is very useful in the treatment of those with hypothyroidism. All of the most recent guidelines of major endocrine societies recommend levothyroxine mono-therapy for first line use in hypothyroidism.

Why does anyone still use desiccated thyroid USP?

The effect on thyroid status of changing from thyroid USP to sodium L-thyroxine was evaluated in 40 patients. With thyroid, abnormally high triiodothyronine (T3) levels were seen in 36 of 38 patients receiving doses of 90 to 240 mg; compared to sodium L-thyroxine, 0.15 to 0.2 mg, the serum T3 was higher (289 +/- 15 ng/dl versus 176 +/- 9 ng/dl, p less than 0.0005) and the thyroxine (T4) lower (7.4 +/- 0.3 microgram/dl versus 11.6 +/- 0.5 microgram/dl, P less than 0.01). Thyrotoxic symptoms occurred in six patients and diminished or disappeared after the change to sodium L-thyroxine, suggesting that the raised T3 level with thyroid may have undesirable effects in some patients. The T4 level, because it is low whether symptoms are present or not, may inadvertently suggest the need for higher dosage of desiccated thyroid in patients who have already received adequate replacement. The dose of sodium L-thyroxine was adequately assessed by measurement of both T4 and T3 levels. Thyroid USP should be discontinued as thyroid medication since it produces thyroid hormone levels that are misleading estimates of thyroid function and can cause thyrotoxic symptoms.

Chronic persistent cough: an uncommon presenting complaint of thyroiditis.

We report two patients with non-conventional thyroiditis whose chief complaint was chronic persistent cough. Cough was attributed to thyroiditis only after extensive diagnostic evaluations failed to uncover another cause and only after cough and thyroiditis disappeared simultaneously with suppressive therapy for the latter. Although thyroiditis is a rare cause of persistently troublesome cough, the diagnosis can be made by systematic evaluation of the sites of receptors and afferent nerves subserving the cough reflex.

Nerve regeneration and thyroid hormone treatment.

On the basis of 3 reports that thyroid hormone treatment stimulates axon outgrowth in rats with nervous system injuries, a 43-year-old patient with an ulnar nerve laceration was given desiccated thyroid (up to 360 mg/day) following nerve suture. The Hoffmann-Tinel sign of sensory axon outgrowth advanced at a rate of 5.0 mm/day in the forearm, approximately 200% faster than the anticipated rate. A good functional result was obtained in 7 months. On the maximum dosage of desiccated thyroid, the patient developed mild weight loss associated with an increased appetite; there was no other sign or symptom of hyperthyroidism. Further investigation of the role of thyroid hormone during nerve regeneration seems warranted.

Suppressive therapy of thyroid nodules in patients with previous radiotherapy to the head and neck.

This is a prospective, randomized study of 431 patients with palpable thyroid nodules who had previous radiotherapy for benign disorders of the head and neck area to determine the response of the thyroid nodules to suppressive therapy and the incidence of thyroid cancer in patients who could not be suppressed and had surgery. A complete response was achieved within 6 months in 18.3 percent of the patients, and in an additional 26 percent of patients between 7 and 12 months postoperatively. Twenty percent of the patients showed complete disappearance of nodules after 1 to 2 years of suppressive therapy. Twenty-two percent who underwent surgery showed carcinoma. If suppressive therapy is to be used, a trial of 1 year rather than 3 or 6 months, as often recommended, may be appropriate.

Lingual thyroid: review, case reports, and therapeutic guidelines.

The literature on lingual thyroid is reviewed. The incidence is relatively rare and sex incidence is four or five to one in favor of females. The embryology and development of the thyroid gland is discussed and some evidence presented to suggest that the lateral thyroid primordia are not involved in the formation of functional thyroid tissue. The pathologic findings of lingual thyroid tissue are similar to that of cervical thyroid tissue, including goiter formation. Diagnostic measures include mirror examination, I-125 scan, and tomography. Thyroid function studies are helpful in evaluating the level of thyroid function. Treatment includes surgical removal, transplantation, I-131, and thyroid replacement. Since the first three methods usually require supplemental thyroid treatment afterward, it is believed that initial thyroid replacement is the treatment of choice since it is simple, safe, effective, and noninvasive. Four new cases are reported.

Plummer's disease with spontaneous progression to hypothyroidism.

A case of Plummer's disease that spontaneously progressed to hypothyroidism is presented. A 49-year-old female visited our hospital because of a 3 kg decrease in body weight during the previous month and a painless nodule in the right anterior area of her neck. A diagnosis of Plummer's disease was made based on the results of thyroid function tests, thyroid scintigrams, and an ultrasonogram, but the patient's disease followed an usual clinical course. About two months later, she gradually developed manifestations of permanent hypothyroidism, and anti-thyroid autoantibodies became positive. In spite of continuous administration of levothyroxine sodium, uptake of 99mTcO4- to the nodule was unchanged or rather increased according to the consecutive thyroid scintigraphies. These results suggested that this case represented an autonomously functioning nodule with underlying silent thyroiditis and Hashimoto's disease.

Raynaud's phenomenon in hypothyroidism.

Two patients with Raynaud's phenomenon were found to be hypothyroid and their symptoms disappeared with thyroid replacement therapy. Vascular reactivity studies in one patient demonstrated decreased vasomotor tone after therapy. Raynaud's phenomenon may be an expression of altered autonomic function in hypothyroidism.

Immunohistochemical study of ACTH and alpha-MSH in vitiligo patients successfully treated with a sex steroid-thyroid hormone mixture.

We previously reported that a sex steroid-thyroid hormone (Metharmon-F; MF, 2 tablets daily) was a potent drug for treatment of vitiligo. Using five patients with generalized vitiligo who were successfully treated with oral administration of MF, we performed an immunohistochemical analysis to elucidate its action mechanism at the cellular level. Histopathologically, the repigmented skin after the treatment showed increased numbers of melanocytes and melanin granules. Immunohistochemically, there was little significant difference between the depigmented lesions before treatment and the repigmented lesion after treatment in terms of the reactivity to adrenocorticotropic hormone (ACTH) and alpha-melanocyte-stimulating hormone (alpha-MSH) in keratinocytes. The immunoreactivity to ACTH in melanocytes both before and after the treatment was minimal, but alpha-MSH in melanocytes became much stronger after the treatment, than before the treatment. The efficacy of MF in treatment of vitiligo was proven to be due to the stimulatory effect of melanocyte proliferation and melanin production via alpha-MSH.

Successful treatment of vitiligo with a sex steroid-thyroid hormone mixture.

Four patients with generalized vitiligo were successfully treated by oral administration of a sex steroid-thyroid hormone (Metharmon-F, 2 tablets daily). Histopathologically, the repigmented skin showed increased numbers of melanocytes and melanin granules in the keratinocytes.

Experience in neonatal screening for congenital hypothyroidism.

From November 1986 to June 1991, 91,683 neonates were screened for congenital hypothyroidism by measuring thyroid-stimulating hormone (TSH). 10,284 neonates were screened with chemical luminoimmunoassay (CLIA), and 80,399 screened with time-resolved fluoroimmunoassay (DELFIA). The critical value of TSH was 20 mU/L. Twenty cases were confirmed to be congenital hypothyroidism. The incidence was 1:4584, with a female to male ratio of 3:2. These patients were treated with thyroid gland desiccant, with a dosage equivalent to L-thyroxin 5-7.5 micrograms/kg/day. Their physical growth and intellectual ability were normal. 81,201 dried blood specimens were tested in single for TSH by DELFIA and T4, T3 and TSH serum testing for those with elevated TSH. No false negative and missing case was found after the screening program started. When frequent fluctuation of T4 and TSH concentration occurred at normal level in some infants, it is better to wait and have a close observation, however the treatment must be started before 3 months of age to avoid the risk of mental retardation.

Vitamin supplements and purported learning enhancement in mentally retarded children.

Dr. Ruth Harrell and her colleagues conducted a study in 1981 in which the administration of high dosages of vitamins were determined to dramatically improve the intellectual functioning of mentally retarded children. This paper documents the efforts of its authors to replicate the Harrell et al. research and, although no significant differences were found between active treatment groups and control groups at study's end, a thorough comparison is made between the two research efforts.

[A case of pituitary hyperplasia associated with primary hypothyroidism].

A thirteen-year-old girl was admitted complaining of short stature and anemia. The low titers of her serum T3 and T4 and the abnormally high TSH level represented primary hypothyroidism. Although she had normal sellar size, CT demonstrated an intra- and suprasellar round mass with homogeneous enhancement. With thyroid replacement therapy the enhanced mass diminished on CT within 5 months, and her symptoms regressed. Twelve cases with radiological diminution of pituitary mass or visual field improvement after thyroid replacement therapy are reviewed. They were considered to be pituitary hyperplasia, rather than pituitary adenoma, caused by long-standing untreated hypothyroidism. In four of them, the pituitary mass on CT was diminished after the therapy. Characteristic CT findings of pituitary hyperplasia, including our case, was a round isodensity mass with homogeneous enhancement in the midline of the pituitary region. In the experimental studies, pituitary hyperplasia is based on the feedback mechanism of hypothalamic-pituitary-thyroid axis, and ultimately autonomous pituitary adenoma may occur. Pituitary mass with hypothyroidism, visual field defect, amenorrhea or galactorrhea tend to be mistaken for prolactinoma or non-functioning adenoma with pituitary hypothyroidism. Thorough endocrinological examination must be carried out. The first choice of treatment for this type of pituitary mass should be thyroid replacement therapy. If there is no improvement of visual field, no regression of pituitary mass on CT, or continuing high TSH levels, then pituitary surgery must be considered.