Clinical Overview > Condition/ Syndrome
Search for other papers by Daramjav Narantsatsral in
Google Scholar
PubMed
Search for other papers by Takagi Junko in
Google Scholar
PubMed
Search for other papers by Iwayama Hideyuki in
Google Scholar
PubMed
Search for other papers by Inukai Daisuke in
Google Scholar
PubMed
Search for other papers by Takama Hiroyuki in
Google Scholar
PubMed
Search for other papers by Nomura Yuka in
Google Scholar
PubMed
Search for other papers by Hirase Syo in
Google Scholar
PubMed
Search for other papers by Morita Hiroyuki in
Google Scholar
PubMed
Search for other papers by Otake Kazuo in
Google Scholar
PubMed
Search for other papers by Ogawa Tetsuya in
Google Scholar
PubMed
Search for other papers by Takami Akiyoshi in
Google Scholar
PubMed
Summary
Dupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature.
Learning points:
-
Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia.
-
Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment.
-
This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.
Search for other papers by Jose León Mengíbar in
Google Scholar
PubMed
Search for other papers by Ismael Capel in
Google Scholar
PubMed
Search for other papers by Teresa Bonfill in
Google Scholar
PubMed
Search for other papers by Isabel Mazarico in
Google Scholar
PubMed
Search for other papers by Laia Casamitjana Espuña in
Google Scholar
PubMed
Search for other papers by Assumpta Caixàs in
Google Scholar
PubMed
Search for other papers by Mercedes Rigla in
Google Scholar
PubMed
Summary
Durvalumab, a human immunoglobulin G1 kappa monoclonal antibody that blocks the interaction of programmed cell death ligand 1 (PD-L1) with the PD-1 and CD80 (B7.1) molecules, is increasingly used in advanced neoplasias. Durvalumab use is associated with increased immune-related adverse events. We report a case of a 55-year-old man who presented to our emergency room with hyperglycaemia after receiving durvalumab for urothelial high-grade non-muscle-invasive bladder cancer. On presentation, he had polyuria, polyphagia, nausea and vomiting, and laboratory test revealed diabetic ketoacidosis (DKA). Other than durvalumab, no precipitating factors were identified. Pre-durvalumab blood glucose was normal. The patient responded to treatment with intravenous fluids, insulin and electrolyte replacement. Simultaneously, he presented a thyroid hormone pattern that evolved in 10 weeks from subclinical hyperthyroidism (initially attributed to iodinated contrast used in a previous computerised tomography) to overt hyperthyroidism and then to severe primary hypothyroidism (TSH: 34.40 µU/mL, free thyroxine (FT4): <0.23 ng/dL and free tri-iodothyronine (FT3): 0.57 pg/mL). Replacement therapy with levothyroxine was initiated. Finally, he was tested positive for anti-glutamic acid decarboxylase (GAD65), anti-thyroglobulin (Tg) and antithyroid peroxidase (TPO) antibodies (Abs) and diagnosed with type 1 diabetes mellitus (DM) and silent thyroiditis caused by durvalumab. When durvalumab was stopped, he maintained the treatment of multiple daily insulin doses and levothyroxine. Clinicians need to be alerted about the development of endocrinopathies, such as DM, DKA and primary hypothyroidism in the patients receiving durvalumab.
Learning points:
-
Patients treated with anti-PD-L1 should be screened for the most common immune-related adverse events (irAEs).
-
Glucose levels and thyroid function should be monitored before and during the treatment.
-
Durvalumab is mainly associated with thyroid and endocrine pancreas dysfunction.
-
In the patients with significant autoimmune background, risk–benefit balance of antineoplastic immunotherapy should be accurately assessed.
Search for other papers by Anna Tortora in
Google Scholar
PubMed
Search for other papers by Domenico La Sala in
Google Scholar
PubMed
Search for other papers by Mario Vitale in
Google Scholar
PubMed
Summary
Reduced intestinal absorption of levothyroxine (LT4) is the most common cause of failure to achieve an adequate therapeutic target in hypothyroid patients under replacement therapy. We present the case of a 63-year-old woman with autoimmune hypothyroidism previously well-replaced with tablet LT4 who became unexpectedly no more euthyroid. At presentation, the patient reported the onset of acute gastrointestinal symptoms characterized by nausea, loss of appetite, flatulence, abdominal cramps and diarrhea, associated with increase of thyrotropin levels (TSH: 11 mIU/mL). Suspecting a malabsorption disease, a thyroxine solid-to-liquid formulation switch, at the same daily dose, was adopted to reach an optimal therapeutic target despite the gastrointestinal symptoms persistence. Oral LT4 solution normalized thyroid hormones. Further investigations diagnosed giardiasis, and antibiotic therapy was prescribed. This case report is compatible with a malabsorption syndrome caused by an intestinal parasite (Giardia lamblia). The reduced absorption of levothyroxine was resolved by LT4 oral solution.
Learning points:
-
The failure to adequately control hypothyroidism with oral levothyroxine is a common clinical problem.
-
Before increasing levothyroxine dose in a patient with hypothyroidism previously well-controlled with LT4 tablets but no more in appropriate therapeutic target, we suggest to investigate non adhesion to LT4 therapy, drug or food interference with levothyroxine absorption, intestinal infection, inflammatory intestinal disease, celiac disease, lactose intolerance, short bowel syndrome after intestinal or bariatric surgery, hepatic cirrhosis and congestive heart failure.
-
LT4 oral solution has a better absorptive profile than the tablet. In hypothyroid patients affected by malabsorption syndrome, switch of replacement therapy from tablet to liquid LT4 should be tested before increasing the dose of LT4.
Search for other papers by Osamah A Hakami in
Google Scholar
PubMed
Search for other papers by Julia Ioana in
Google Scholar
PubMed
Search for other papers by Shahzad Ahmad in
Google Scholar
PubMed
Search for other papers by Tommy Kyaw Tun in
Google Scholar
PubMed
Search for other papers by Seamus Sreenan in
Google Scholar
PubMed
Search for other papers by John H McDermott in
Google Scholar
PubMed
Summary
Immune checkpoint inhibitors (ICIs) have revolutionised cancer therapy and improved outcomes for patients with advanced disease. Pembrolizumab, a monoclonal antibody that acts as a programmed cell death 1 (PD-1(PDCD1)) inhibitor, has been approved for the treatment of advanced melanoma and other solid tumours. Immune-related adverse events (irAEs) including endocrinopathies have been well described with this and other PD-1 inhibitors. While hypothyroidism and hyperthyroidism, and less commonly hypophysitis, are the most common endocrinopathies occurring in patients treated with pembrolizumab, the incidence of type 1 diabetes mellitus (T1DM) was low in clinical trials. We report a case of pembrolizumab-induced primary hypothyroidism and T1DM presenting with severe diabetic ketoacidosis (DKA). A 52-year-old male patient was treated with pembrolizumab for metastatic melanoma. He presented to the emergency department with a 1-day history of nausea and vomiting 2 weeks after his seventh dose of pembrolizumab, having complained of polyuria and polydipsia for 2 months before presentation. He had been diagnosed with thyroid peroxidase (TPO) antibody-negative hypothyroidism, requiring thyroxine replacement, shortly after his fifth dose. Testing revealed a severe DKA (pH: 6.99, glucose: 38.6 mmol/L, capillary ketones: 4.9 and anion gap: 34.7). He was treated in the intensive care unit as per the institutional protocol, and subsequently transitioned to subcutaneous basal-bolus insulin. After his diabetes and thyroid stabilised, pembrolizumab was recommenced to treat his advanced melanoma given his excellent response. This case highlights the importance of blood glucose monitoring as an integral part of cancer treatment protocols composed of pembrolizumab and other ICIs.
Learning points:
-
The incidence of T1DM with pembrolizumab treatment is being increasingly recognised and reported, and DKA is a common initial presentation.
-
Physicians should counsel patients about this potential irAE and educate them about the symptoms of hyperglycaemia and DKA.
-
The ESMO guidelines recommend regular monitoring of blood glucose in patients treated with ICIs, a recommendation needs to be incorporated into cancer treatment protocols for pembrolizumab and other ICIs in order to detect hyperglycaemia early and prevent DKA.
Search for other papers by Ploutarchos Tzoulis in
Google Scholar
PubMed
Search for other papers by Richard W Corbett in
Google Scholar
PubMed
Search for other papers by Swarupini Ponnampalam in
Google Scholar
PubMed
Search for other papers by Elly Baker in
Google Scholar
PubMed
Search for other papers by Daniel Heaton in
Google Scholar
PubMed
Search for other papers by Triada Doulgeraki in
Google Scholar
PubMed
Search for other papers by Justin Stebbing in
Google Scholar
PubMed
Summary
Five days following the 3rd cycle of nivolumab, a monoclonal antibody, which acts as immune checkpoint inhibitor against the programmed cell death protein-1, for metastatic lung adenocarcinoma, a 56-year-old woman presented at the hospital critically ill. On admission, she had severe diabetic ketoacidosis (DKA), as evidenced by venous glucose of 47 mmol/L, blood ketones of 7.5 mmol/L, pH of 6.95 and bicarbonate of 6.6 mmol/L. She has had no personal or family history of diabetes mellitus (DM), while random venous glucose, measured 1 week prior to hospitalisation, was 6.1 mmol/L. On admission, her HbA1c was 8.2% and anti-GAD antibodies were 12 kIU/L (0–5 kU/L), while islet cell antibodies and serum C-peptide were undetectable. Nivolumab was recommenced without the development of other immune-mediated phenomena until 6 months later, when she developed hypothyroidism with TSH 18 U/L and low free T4. She remains insulin dependent and has required levothyroxine replacement, while she has maintained good radiological and clinical response to immunotherapy. This case is notable for the rapidity of onset and profound nature of DKA at presentation, which occurred two months following commencement of immunotherapy. Despite the association of nivolumab with immune-mediated endocrinopathies, only a very small number of patients developing type 1 DM has been reported to date. Patients should be closely monitored for hyperglycaemia and thyroid dysfunction prior to and periodically during immunotherapy.
Learning points:
-
Nivolumab can induce fulminant type 1 diabetes, resulting in DKA.
-
Nivolumab is frequently associated with thyroid dysfunction, mostly hypothyroidism.
-
Nivolumab-treated patients should be monitored regularly for hyperglycaemia and thyroid dysfunction.
-
Clinicians should be aware and warn patients of potential signs and symptoms of severe hyperglycaemia.
Search for other papers by Sulaiman Haji Ali in
Google Scholar
PubMed
Search for other papers by K Aljenaee in
Google Scholar
PubMed
Search for other papers by W A Wan Mahmood in
Google Scholar
PubMed
University College Dublin, Dublin, Ireland
Search for other papers by M Hatunic in
Google Scholar
PubMed
Summary
Hypothyroidism is a recognized side effect of thalidomide drugs. We herein report a case of 83-year-old Irish female with a diagnosis of multiple myeloma and a background history of type 2 diabetes mellitus and hypertension. Our patient received pomalidomide and multiple courses of chemotherapy and achieved very good initial response for her multiple myeloma but subsequently she relapsed. She did not have any past history of thyroid disease or family history of thyroid disorders. Prior to treatment with pomalidomide, her thyroid function test was completely normal. She was commenced on pomalidomide in February 2017. Four weeks post treatment, she presented with worsening fatigue, and as a part of her workup, a thyroid function test was performed. Her free T4 was low at 7.2 pmol/L (reference range: 9.0–20.0) while her TSH was elevated at 44.7 mIU/L (reference range: 0.35–4.94). Pomalidomide treatment was terminated, and she was commenced on thyroid hormonal therapy replacement therapy with thyroxine with good clinical and biochemical response. Practitioners prescribing pomalidomide should be aware of this potential complication and patients who are receiving immunomodulatory drugs like pomalidomide should undergo regular thyroid hormone levels screen.
Learning points:
-
Overt hypothyroidism is a side effect of pomalidomide.
-
Thyroid function test should be included as a screening test with regular review in patients receiving pomalidomide.
-
Unexplained worsening fatigue in patients receiving pomalidomide should raise the possibility of overt hypothyroidism.
Search for other papers by Luísa Correia Martins in
Google Scholar
PubMed
Search for other papers by Ana Rita Coutinho in
Google Scholar
PubMed
Search for other papers by Mónica Jerónimo in
Google Scholar
PubMed
Search for other papers by Joana Serra Caetano in
Google Scholar
PubMed
Search for other papers by Rita Cardoso in
Google Scholar
PubMed
Search for other papers by Isabel Dinis in
Google Scholar
PubMed
Search for other papers by Alice Mirante in
Google Scholar
PubMed
Summary
Alternating between hyper- and hypo-thyroidism may be explained by the simultaneous presence of both types of TSH receptor autoantibodies (TRAbs) – thyroid stimulating autoantibodies (TSAbs) and TSH blocking autoantibodies (TBAbs). It is a very rare condition, particulary in the pediatric age. The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time. Many mechanisms may be involved in fluctuating thyroid function: hormonal supplementation, antithyroid drugs and levels of TSAbs and TBAbs. Frequent dose adjustments are needed in order to achieve euthyroidism. A definitive therapy may be necessary to avoid switches in thyroid function and frequent need of therapeutic changes. We describe an immune-mediated case of oscillating thyroid function in a 13-year-old adolescent. After a short period of levothyroxine treatment, the patient switched to a hyperthyroid state that was only controlled by adding an antithyroid drug.
Learning points
-
Autoimmune alternating hypo- and hyper-thyroidism is a highly uncommon condition in the pediatric age.
-
It may be due to the simultaneous presence of both TSAbs and TBAbs, whose activity may be estimated in vitro through bioassays.
-
The clinical state of these patients is determined by the balance between TSAbs and TBAbs and can change over time.
-
The management of this condition is challenging, and three therapeutic options could be considered: I-131 ablation, thyroidectomy or pharmacological treatment (single or double therapy).
-
Therapeutic decisions should be taken according to clinical manifestations and thyroid function tests, independent of the bioassays results.
-
A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment. A definitive treatment might be considered due to the frequent switches in thyroid function and the need for close monitoring of pharmacological treatment.
Search for other papers by Mahmud Abo Salook in
Google Scholar
PubMed
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for other papers by Carlos Benbassat in
Google Scholar
PubMed
Search for other papers by Yulia Strenov in
Google Scholar
PubMed
Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel
Search for other papers by Amit Tirosh in
Google Scholar
PubMed
Summary
A 55-year-old male, with a positive medical history for hypothyroidism, treated with stable doses for years was admitted with subacute thyroiditis and a feeling of pain and pressure in the neck. Laboratory tests showed decrease in TSH levels, elevated erythrocyte sedimentation rate, and very high antithyroid antibodies. Owing to enlarging goiter and exacerbation in the patient's complaints, he was operated with excision of a fibrotic and enlarged thyroid lobe. Elevated IgG4 plasma levels and high IgG4/IgG plasma cell ratio on immunohistochemistry led to the diagnosis of IgG4-mediated thyroiditis. We concluded that IgG4-thyroiditis and IgG4-related disease should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.
Learning points
-
IgG4-related disease is a systemic disease that includes several syndromes; IgG4-related thyroiditis is one among them.
-
IgG4-thyroiditis should be considered in all patients with an aggressive form of Hashimoto's thyroiditis.
-
Patients with suspected IgG4-thyroiditis should have blood tested for IgG4/IgG ratio and appropriate immunohistochemical staining if possible.
