Case Report- A 51 year old male of Indian origin, known case of
hyperthyroidism on anti-thyroid drug (carbimazole) since 4 weeks, was
brought to the emergency department of Maharaja Agrasen Hospital on
04-05-2019 with the complaints of: stretching and stiffening of hands,
upward rotation of eyeballs and frothing from mouth. On investigation
the plasma glucose level was found to be 52mg/dl. Intravenous 25%
dextrose reversed the symptoms. There was no family history of diabetes.
Neurology reference was done and subsequent Electroencephalogram
revealed normal study. Patient had recurrent hypoglycemia for which
endocrinology reference was done. The results of investigation dated
07-05-2019 were- C-PEPTIDE SERUM = 10.28ng/mL (0.81-3.85ng/mL),INSULIN ANTIBODIES = >300U/mL (<12.0
U/mL), SERUM INSULIN RANDOM = 241.9µU/mL (<140
µU/mL). Thyroid Function Test dated 24-05-2019 reveals TSH
<0.01µIU/ml (0.3-5.5 µIU/ml), T3 = 362ng/dl (60-200 ng/dl), T4
= 18.4µg/dl (4.5-12 µg/dl). On CECT abdomen triple phase revealed
pancreas in normal size, shape, outline and attenuation, no focal lesion
seen. Patient was treated with 10 mCi of radioactive iodine (I – 131)
in June 2019. Current thyroid profile report dated 22-08-2019 is TSH=
3.3µIU/ml (0.3-5.5 µIU/ml), T3 = 1.1ng/ml (0.4-1.81ng/mL), T4 = 7.9µg/dl
(4.5-12 µg/dl). Thyroid profile dated 14.10.2019 shows patient going
into post radioactive iodine ablation hypothyroidism with TSH=
113.67µIU/ml (0.3-5.5 µIU/ml), T3 = <0.10ng/ml
(0.4-1.81ng/mL), T4 = <0.30µg/dl (4.5-12 µg/dl).
Discussion-Clinically, IAS present with symptoms of hypoglycemia, which can
manifest either in the postprandial or in the post absorptive phases.
This disease has no gender predilection. Its onset is quite often
dramatic. Paradoxically, hyperglycemia can occur after a meal or glucose
challenge.4 In such
patients, total serum insulin levels are very high as compared to those
seen in the patients of insulinoma, in as much as insulin levels are
just inappropriate and rarely more than 100 mU/L in the latter
category.3 However, serum-free insulin level may be
normal or high with incomplete suppressed plasma C-peptide level. In
such cases, serum proinsulin levels have also been noted to be very
high. Insulin antibodies are typically polyclonal, although monoclonal
antibodies have also been
described.5 IAS has been
observed to be associated with the usage of drugs like insulin,
sulfonylureas; SH-containing medicines (methimazole, captopril,
penicillamine etc.), hydralazine, procainamide, isoniazid and
α-interferone etc., in association with autoimmune disorders, plasma
cell dyscrasias, alcoholic liver disease and organ transplant
patients.5 The disease is self-limiting in most of the
cases. Most of the patients respond to small frequent meals - six or
more times - in a day. Alfa-glucosidase inhibitors may sometimes be
helpful in decreasing the postprandial levels of immunoreactive insulin
resulting in reducing postprandial hypoglycemic episodes. Such patients
who did not respond to the Alfa-glucosidase were treated with
prednisolone, diazoxide, octreotide and plasmapheresis, with variable
results. In the backdrop of the foregoing
analytic review of the facts described above, it may be possible that
the incidence of hypoglycemia has been part of the natural course of the
disease, which is corroborated by the fact that there was spontaneous
remission in 189 of 226 (83.6%) Japanese patients.4The exact mechanism of hypoglycemia in IAS is not known, but it is
postulated that sulphydryl group interacts with disulfide bond in the
insulin molecule, making the later more immunogenic. Most of the cases
reported in Japan was because of the use of sulphhydryl group-containing
drugs, while cases reported from other parts of the world are more
frequently associated with autoimmune diseases or plasma cell
dyscrasias.3 Our patient was taking drug that
contained sulfur and hydrogen atoms, namely carbimazole. Carbimazole is
a prodrug that gets converted to the active form i.e., Methimazole. This
activated form reacts by covalent binding with sulfhydryl group of
cysteines. Thus it can be postulate that the activated form of
sulfonamide may bind with disulfide bond in the insulin molecule, making
the latter more immunogenic.
Corresponding Author details - Dr Himanshu Jaiswal, MBBS, DRM
Final Year Resident.
Mailing Address- Institute of Nuclear Medicine & Allied Sciences,
Timarpur, Delhi 110054, India.
Email- himanshu9599@gmail.com