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.

Thyroglobulin (Tg) monitoring is the biochemical standard for surveillance of recurrent differentiated thyroid cancer (DTC). Several assays are available to quantify Tg levels: immunometric assay (IMA), radioimmunoassay (RIA), and the newer liquid chromatography tandem mass spectrometry (LC-MS). It is well known that a number of entities can interfere with the accuracy of testing, and at this point in time, no one assay perfectly balances high sensitivity with low risk of interference. In this case study, we present two cases in which treatment with desiccated thyroid extract (Armour thyroid) led to a sudden elevation in Tg, which resolved when Armour thyroid was discontinued. This elevation occurred when Tg was measured with both IMA and LC-MS, which suggests direct interference from porcine Tg rather than heterophilic or thyroglobulin antibody (TgAb) interference. We suggest that patients with a history of DTC not be treated with desiccated thyroid extracts consistent with guidelines. Furthermore, more advances need to be made in the area of Tg testing to improve specificity and avoid detection of nonhuman Tg and other similar proteins.

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.

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.

Around 5-10% of hypothyroid patients continue to experience profound and sometimes disabling symptoms, including fatigue, depression and impaired cognition, in spite of being adequately replaced biochemically. The use of the combination of levothyroxine and liothyronine and natural desiccated thyroid extract is controversial for reasons of costs, a lack of evidence of additional benefit over levothyroxine alone, and potential safety concerns. Clinical guidelines caution against the use of both, and advise that only in exceptional cases may a short trial be considered. Natural desiccated thyroid extract is not licensed for use in the UK. However, key deficiencies in the existing evidence-base together with improved understanding of the pharmacology of levothyroxine resistance, indicates that now is the right time for a definitive clinical trial to address this important area of uncertainty.

Armour® Thyroid (Forest Pharmaceuticals, LLC; affiliate of Allergan, Dublin, Ireland) is a natural porcine derivative thyroid supplement that is frequently used without physician monitoring by health enthusiasts as a weight loss supplement. Although there are no publications associating Armour Thyroid and major coronary events, significant drug interactions may exist. A 32-year-old male with a history of hypothyroidism, cystic acne, and solitary congenital kidney presented to the emergency room after experiencing crushing substernal chest pain radiating to his left shoulder, accompanied by diaphoresis and shortness of breath. The patient denied any tobacco use or family history of heart disease. He was self-administering 120 mg of Armour Thyroid daily. On examination, the patient was well-developed with cystic acne and a flushed appearance. His vital signs on admission were a blood pressure of 171/106 mmHg, heart rate of 88 beats per minute (bpm), and respiratory rate of 16 breaths/min. The electrocardiogram revealed marked ST-segment elevation in the anterior chest leads. Laboratory studies revealed elevated troponins. Urine drug screen was negative. The patient underwent an emergent coronary angiogram, which confirmed an occluded left anterior descending artery. He was treated successfully by thrombectomy and stenting of his left anterior descending artery. Evaluation for other causes of thrombosis was negative: glycosylated hemoglobin (HbA1C) 5.5%, low-density lipoprotein (LDL) 127 mg/dL, high-density lipoprotein (HDL) 33 mg/dL, hypercoagulable evaluation negative, and hemoglobin (Hgb) 17.1 gm/dL. Luteinizing hormone (LH) and follicle stimulating hormone (FSH) were < 0.20 miu/mL. Thyroid profile results were thyroid-stimulating hormone (TSH) 0.20 miu/mL (low), T3 free 4.08 pg/mL (high), and T4 total 1.2 mcg/dL (low), which were consistent with exogenous thyroid hormone administration. Focused questioning triggered by his cystic acne led to the discovery that the patient was self-administering exogenous testosterone replacement therapy. The patient declined to share specifics with the healthcare team. This was confirmed by a high testosterone level of 1,311 ng/dL. Hyperthyroidism increases the risk of cardiovascular events two to three times through the propagation of a hypercoagulable, hypofibrinolytic state possibly via an increase in clotting factors, a decrease in fibrinolytic enzymes, and an increased inhibition of the protein C pathway. The effect of androgens on cardiovascular mortality is uncertain. Androgens stimulate the hemostatic system, increase adverse lipid profile, and erythropoiesis. The combined therapy likely resulted in a synergistic potentiation of hypercoagulable, hypofibrinolytic effects of both agents. Given the absence of other cardiovascular risk factors, the cause of the myocardial infarction in our patient was likely due to drug interaction between Armour Thyroid and exogenous testosterone therapy. Due to the potential drug interaction between both natural and prescribed thyroid hormone and testosterone supplements, patients should be discouraged from self-administration of thyroid or anabolic steroids. Due to the lack of standardization in the T3 content, the use of Armour Thyroid should be avoided.