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.

Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism.

BACKGROUND: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice. METHODOLOGY/PRINCIPAL FINDINGS: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈) 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation. CONCLUSIONS/SIGNIFICANCE: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.

Manipulating thyroid status alters endoplasmic reticulum calcium homeostasis in rat cerebellum.

Thyroid-related hormones regulate the efficiency and expression of sarco-endoplasmic reticulum calcium ATPases in cardiac and skeletal muscle. However, little is known about the relationship between thyroid hormones and calcium (Ca2+) homeostasis in the brain. It is hypothesized that manipulating rat thyroid hormone levels would induce significant brain Ca2+ adaptations consistent with clinical findings. Adult male Sprague-Dawley rats were assigned to one of three treatment groups for 28 days: control, hypothyroid (6-n-propyl-2-thiouracil (PTU), an inhibitor of thyroxine (T4) synthesis), and hyperthyroid (T4). Throughout, rats were given weekly behavioral tests. Ca2+ accumulation decreased in the cerebellum in both hyper- and hypothyroid animals. This was specific to different ER pools of calcium with regional heterogeneity in the response to thyroid hormone manipulation. Behavioral tasks demonstrated sensitivity to thyroid manipulation, and corresponded to alterations in calcium homeostasis. Ca2+ accumulation heterogeneity in chronic hyper- and hypothyroid animals potentially explains clinical manifestations of altered thyroid status.

[The effect of estrogen and, sex-steroids and thyroid hormone preparation on bone mineral density in senile osteoporosis--a comparative study of the effect of 1 alpha-hydroxycholecalciferol (1 alpha-OHD3) on senile osteoporosis].

In order to assess the effect of sex steroids on bone mineral density in Japanese with senile osteoporosis, the bone mineral density in 1/3 distal site of radius was measured serially before and after treatment for 2 years using single photon absorptiometry. Sixty seven old females with senile osteoporosis were divided into 4 groups, Group 1 (n = 28, mean age; 74.4 +/- 1.3 y.o., mean +/- SEM) was the control group, Group 2 (n = 14, mean age; 73.7 +/- 1.7 y.o.) was treated with 0.5-1.0 micrograms/day of 1 alpha -OHD3, Group 3 (n = 12, mean age; 75.4 +/- 2.9 y.o.) was treated with conjugated estrogen (Premarin) in a dose of 0.3125 mg/day (3 approximately 4 weeks administration followed by 1 week rest) and Group 4 (n = 13, mean age; 76.4 +/- 1.8 y.o.) was treated with sex-steroids (pregnenolone : androstenedione : androstenediol : testosterone : estrone = 1.0 mg : 1.0 mg : 0.5 mg : 0.1 mg : 5 micrograms/tablet) and thyroid hormone (thyroid-sicca 7.5 mg/tablet) preparation in a dose of 2 tablets/day. When the radial bone mineral density (RMD) before the treatment was taken as 100%, RMDs of each group at 6, 12, 18 and 24 months were 96.4 +/- 3.1%, 97.3 +/- 2.0%, 93.7 +/- 2.1% and 96.1 +/- 1.8% in Group 1, 100.8 +/- 2.8%, 106.4 +/- 2.1%, 101.3 +/- 3.4% and 108.8 +/- 2.9% in Group 2, 103.0 +/- 2.8%, 106.2 +/- 3.5%, 105.9 +/- 4.3% and 100.2 +/- 4.7% in Group 3, 105.3 +/- 2.2%, 104.7 +/- 2.3%, 112.6 +/- 6.4% and 112.1 +/- 6.7% in Group 4, respectively. Therefore, significant increases in RMD were observed in Groups 2, 3 (transient) and 4 when compared with Group 1. In Group 3, serum level of parathyroid hormone (PTH) was significantly (p less than 0.05) increased from 0.28 +/- 0.03 ng/ml before the treatment to 0.55 +/- 0.15 ng/ml at 24 months after the treatment. In Group 2, transient (6 months after the treatment) but significant (p less than 0.01) increase in urinary Ca/Creatinine ratio from 0.15 +/- 0.04 to 0.20 +/- 0.03 was found. Serum A1-P activities in Group 4 was shown to increase transiently from 131 +/- 10 IU to 151 +/- 12 IU (p less than 0.05) at 6 months and to 158 +/- 13 IU (p less than 0.01) at 12 months followed by subsequent decrease to 135 +/- 6 IU at 18 months and 133 +/- 10 IU at 24 months after the treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

The fall in the incorporation of labelled iron into the bone marrow during enhanced erythropoiesis: this paradox explained by changes in ferrokinetics and cytokinetics using the model of mice affected by thyroid hormones.

Using the model of mice affected by thyroid hormones, a ferrokinetic analysis was made of the repeatedly observed paradoxical fall in the incorporation of labelled iron into the bone marrow under conditions of the overall stimulation of erythrocyte formation.

Ultrastructure of the choroid plexus epithelium of pigeons treated with drugs: I. Effect of Thyradin, 2,4-dinitrophenol, and cycloheximide.

Possible changes in the epithelial cells of the pigeon choroid plexus induced by administration of thyroid powder (Thyradin), 2,4-dinitrophenol, and cycloheximide were studied by scanning and transmission electron microscopy. A marked increase in the number of large bulbous and bleblike protrusions on the apical end of the epithelial cells was observed after oral administration of Thyradin for a month. The endoplasmic content of the protrusions consisted mainly of electron-lucent material. These results provide morphological evidence for the stimulatory effect of Thyradin. Intramuscular injections of 2,4-dinitrophenol for 15 days caused the collapse or deformation of the mitochondria and bleblike or bulbous protrusions. This indicates that changes in the surface configuration of the choroid plexus are controlled by an energy-dependent mechanism. The decrease of protrusions and polyribosomes and increase of the tubular saccules of varying electron density, size, and shape were noted in cells after 15 days of intramuscular cycloheximide injection. The electron density of the protrusions is lower than that of the control pigeons. The results of this study suggest that a curious pleomorphic structure on the apical surface of the choroid epithelial cell of pigeon is closely related to the functional state of choroidal cells. The study also demonstrates that a secondary ultrastructural response due to diverse physiologic effects is reflected in the architecture of the choroid plexus cells.

Adrenal changes in genetically hypothyroid mice.

The adrenocortical X-zone was very poorly developed in young female mice homozygous for the hypothyroid, hyt, mutation, Feeding the mice thyroid powder resulted in the development of an X-zone. This subsequently degenerated in the same way as the X-zone found in the normal litter-mates of the mutants. We suggest that the adrenocortical effects may be due to changes in prolactin stimulation consequent upon the lack of response to thyrotrophin of the mutants.

The effects of desiccated thyroid on the rat lung.

Pressure-volume characteristics of whole lungs were measured in euthyroid rats and in rats fed 0.4% desiccated thyroid for eight weeks. The lungs were degassed by incising the diaphragm after the animals had breathed 100% oxygen for ten minutes. The pressure-volume characteristics were measured by inflating and deflating the lungs at a rate of 3.5 cc/min. Total lung capacity (TLC) was considered to be that volume of air required to produce a transpulmonary pressure of 30 cm H2O. At TLC there was 35% greater lung volume in the thyroid-treated animals than in their littermate controls. Similar results were observed in saline-filled lungs. Alveolar surface are (Sa) increased from 0.28m2 in the lungs of control animals to 0.75m2 in lungs of thyroid-treated animals. There was an 85% increase in the alveolar surface density (SVa) in the thyroid-treated animals. These results, obtained by morphometric analysis, suggest that greater lung volume in the thyroid-treated animals resulted from alveolar hyperplasia or "partitioning."

Reactions of hypothalamic ascorbic acid, serum ceruloplasmin and the adenohypophysis to oestradiol: inhibition by L-thyroxine.

Four weeks' administration of oestradiol benzoate to male and female rats in doses of 1 mg twice a week leads to adenohypophyseal hyperplasia and to an increase in the thyroxine-binding capacity of the adenohypophyseal proteins in vitro. At the same time, serum polyphenol oxidase (ceruloplasmin) activity rises and the hypothalamic ascorbic acid concentration falls. The simultaneous administration of L-thyroxine (0.1 mg/rat/per day) or dried thyroid (but not D-thyroxine) significantly inhibits these changes (adenohypophysis, ceruloplasmin) or completely suppresses them (hypothalamic ascorbic acid). L-thyroxine evidently blocks the action of oestradiol in the adenohypophysis, the liver and the hypothalamus; the significance of this inhibition is discussed in relation to dopaminergic modulation of the adenohypophyseal reaction to oestradiol.

Influence of the thyroid hormones on erythropoiesis and radiation resistance in C 57 black mice.

Oral administration of dried thyroid gland to C57Bl adult male mice in a dose of 0.6 g per 100 g diet during 10 days increased the metabolic rate and stimulated the erythropoiesis. Three to six days after thyroid pretreatment the radiation resistance of the mice increased, as revealed by their 30-day survival and a higher recovery of peripheral blood cell counts. The period of increased resistance to radiation was correlated with the receding of hypermetabolic effects and with the increase of repopulating abilities of the bone marrow cells.

Uptake of thallium-201 in enlarged thyroid glands: concise communication.

We have investigated the thyroid uptake of Tl-201 in 37 patients with various types of goiter, and in six with normal thyroids. Significant thallium uptake was found in all cases in which there was thyroid enlargement, including Graves' disease, toxic thyroid nodule, primary hypothyroidism, simple goiter, Hashimoto's disease, thyroid carcinoma, and thyroid adenoma. If goiter was absent, however, there was no demonstrable uptake--e.g., in secondary hypothyroidism, subacute thyroiditis, and the normal controls. Thallium uptake did not correlate with thyroid function tests such as BMR, T3-RU, T3, T4, TSH, antithyroid antibodies, or the 24-hr I-131 uptake. In 23 patients with diffuse goiter, on the other hand, maximum Tl-201 uptake correlated well with thyroid weight: r = 0.836 (p less than 0.001); y = 0.02 x + 0.06.

Effect of hyperthyroidism on haemopoietic stem cell kinetics in mice.

Changes in the pool of haemopoietic colony-forming units (CFUs) of bone marrow and spleen were studied in experiments with mice fed dried thyroid gland (TH) for 21 days, and during the 13 days that followed feeding. After HU treatment, the number of CFUs in DNA synthesis was estimated. As early as the second day of TH treatment, the pool of CFUs is gradually increased, leading to an increase in the total number of splenic and bone marrow CFUs persisting after TH treatment for the period examined. Simultaneously, the numbers of nucleated cells in the bone marrow and spleen are increased. During TH feeding and following its termination, the total number of erythrocytes and the haematocrit values did not change significantly, whereas an increased number of leucocytes was observed in the peripheral blood after TH treatment. Elevation of the proliferative activity of CFUs occurred early in the period of TH treatment, with the maximum attained by end of the first week of TH feeding. This suggests a rapid response of the haemopoietic stem cell compartment to the administration of TH hormones. The participation of humoral factors controlling CFUs compartments in the mechanism of the stimulatory effect of TH hormones on haemopoietic stem cells is discussed.

Effect of interaction of oestrogen, testosterone and thyroid hormones on the serum ceruloplasmin level in rats.

Male rats were given oestradiol benzoate (1 mg as an aquaeous microcrystal suspension i.m. twice a week), testosterone isobutyrate (0.5 mg as an aquaeous microcrystal suspension i.m. once a week) and dried thyroid (Thyreoidin SPOFA, 0.2% in food), alone or variously combined. Oestradiol raised adenohypophyseal weight, the binding capacity of the adenohypophyseal proteins for thyroxine and the serum ceruloplasmin level. Testosterone and Thyreoidin inhibited all three of these reactions, but when they were administered together there was no summation of their inhibitory action. The nature of the relationships between the three given proteosynthetic reactions is discussed.