Patient S., 34 years old, was admitted to the Endocrinology Research Centre (ERC) in September 2021 with a diagnosis of hypothyroidism and DM. On admission she complained of impaired swallowing, sore throat, "twitching" pain in the neck, hoarseness of voice, episodic headaches, periorbital swelling mainly in the morning, high glycemia indexes up to a maximum of 34 mmol/l, numbness and swelling of lower extremities.
On examination: the general condition was relatively satisfactory, oriented in space and time, contact was easy; body type was hypersthenic, body weight 95 kg, height 166 cm, body mass index 35.19 kg/sq.m. (II degree obesity); on the back there were areas of vitiligo; on the skin of the front surfaces of both thighs there were rough scars (according to the patient, post-injection abscesses); on other organs and systems without special features; the patient's appearance was unkempt, her clothes and hair were dirty.
In the life history: three childbirths; smoker; DM in a paternal relative. The patient does not work (education: engineer).
According to the medical history of the patient, since the summer of 2020 the patient had been suffering from sore throat, tonsillitis diagnosed, treated with various antibacterial drugs - without positive effect. In October 2020, subacute thyroiditis was diagnosed. She was treated with prednisolone 30 mg/day for about a month with effect. In November 2020, hypothyroidism was diagnosed based on the results of hormonal blood tests, and she was prescribed levothyroxine sodium 50 mcg. Further, due to decompensation of hypothyroidism, the dose of levothyroxine was gradually increased. In February 2021, severe sore throat, reappointed prednisolone at a dose of 60 mg a day, received for 2 months with gradual withdrawal by the end of July 2021. After withdrawal of the drug, she again experienced a worsening of her well-being: complaints of impaired swallowing, hoarseness of the voice. In the blood test of August 14, 2021 (against the background of taking 200 mcg of levothyroxine sodium): TSH 144 mcMU/ml, free T4 was not investigated. Thyroid gland ultrasound investigation of in September 2021: volume 59 ml, thyroiditis pattern. Examination in a specialized medical institution was recommended.
In addition, according to the medical records, in March 2021 there was an episode of unconsciousness, an ambulance team was called, and she was hospitalized with hyperglycemia of 26 mmol/l. Intensive insulin therapy (Insulin lispro 8–35 units 3 times a day, Insulin-isophan 30 units in the morning and in the evening) was initiated at the hospital. After discharge, due to complaints of high glycemia, Metformin was added to therapy (received 1000 mg in the morning and evening) - no effect, glycemia up to 34 mmol/l on self-measurement. Recommendation for examination in a specialized medical institution.
Against the background of taking Prednisolone, she has noted weight gain, since March 2021, of about 40 kg (weight in August 2021 − 100 kg).
On September 21, 2021, she was hospitalized for the first time at the ERC. Decompensation of primary hypothyroidism against the background of autoimmune thyroiditis was confirmed: TSH 108 mE/l, AT to TPO > 1000 ME/ml, AT to TG > 40000 ME/ml, free T4 < 5.15 pmol/l. Thyroid ultrasound: volume 42 ml, signs of autoimmune thyroiditis (according to CT scan, the trachea is not displaced). The dose of levothyroxine sodium was increased to 300 mcg. Under medical supervision, the free T4 level was normalized at 11.29 pmol/l for 5 days.
Discordant glycemia from 33 mmol/l to 2.1 mmol/l according to a glucometer (no hyperglycemia was registered in venous blood), HbA1c 5.2% were noted in the department against the background of insulin therapy. At hyperglycemia, there were no ketones in the urine. Taking into account alternating hyper- and hypoglycemia, presence of autoimmune diseases (thyroiditis, vitiligo) and suspicion of autoimmune diabetes, DM in a relative of the patient, as well as to exclude insulin autoimmune syndrome, antibodies to insulin, glutamate decarboxylase, tyrosine phosphatase were examined - normal. Additional hormonal blood tests were performed: ACTH 13.38 pg/ml, cortisol 499 nmol/l, IGF1 121.3 ng/ml - adrenal insufficiency and tumor producing insulin-like growth factor 2 were unlikely (IGF1 levels were usually suppressed to 100 ng/ml or less in such tumors).
On September 22, 2021 she was transported to the intensive care unit due to an episode of mental confusion, accompanied by nausea, vomiting, headache, with a background glycemia of 3.2 mmol/L. In the intensive care unit, glycemia readings were within 4.5–8.3 mmol/l for 2 days against the background of complete withdrawal of insulin therapy and metformin, with intravenous injection of glucose solution (then the glucose-lowering therapy was not resumed). According to multi-slice computed tomography (MSCT) of the brain: no pathological changes were revealed, heterogeneity of the pituitary gland structure. Presence of type 1 DM, taking into account clinical picture and C-peptide level of 2.05 ng/ml, is unlikely. An oral glucose tolerance test (OGTT) was performed: no evidence of DM was obtained: fasting glucose 4.96 mmol/l, 2 hours later 7.39 mmol/l. Thus, artifical hypo- and hyperglycemia was suspected.
Continuous interstitial glycemia monitoring was performed (Fig. 1). Elevated glucose values (up to 18 mmol/L) were recorded only by glucometer, when no clinically significant hyperglycemia was detected in the interstitial fluid at one time (Fig. 2): glucose from 2.4 to 8.1 mmol/L.
Hypoglycemic states were repeatedly noted (Fig. 3), and in one such episode venous blood sampling was performed: glucose 1.86 mmol/l, insulin 2.2 µU/ml, C-peptide 1.18 ng/ml, substance of sugar-lowering drugs by tandem mass spectrometry was not found, proinsulin less than 0.5 pmol/l (Table 1). Taking into account discordant values of insulin and C-peptide (insulin level is typical for hypoinsulinemic variant of hypoglycemia, and C-peptide level for hyperinsulinemic variant), it was decided to perform a fasting test to re-examine these hormones against hypoglycemia.
Figure 2. Glycemic discrepancy between glucometer readings and continuous interstitial glycemic monitoring system readings.
Table 1
The Patient’s Laboratory Data on Spontaneous Hypoglycemic Episode
Test | Value (units) | Reference interval |
Glucose | 1,86 mmol/l | 3.1–6.1 |
Insulin | 2.2 µU/ml | 2.6-24.91 |
Substances of blood glucose-lowering drugs | - | |
С-peptide | 1,18 ng/ml | 1.1–4.41 |
Proinsulin | < 0.5 pmol/l | 0.70–4.301 |
1 - Reference interval for euglycemia |
The fasting test was completed 1.5 hours after the meal, venous blood values were consistent with hyperinsulinemic hypoglycemia, and insulin was tested with the kit RE. Since the laboratory data were borderline, this blood sample was tested with the kit AA (Table 2).
Table 2
The Patient’s Laboratory Data at the end of the Fasting Test
Test | Value (units) | Reference interval |
Glucose | 1,64 mmol/l | 3.1–6.1 |
Insulin (RE)* | 3,16 µU/ml | 2.6-24.91 |
Insulin (AA) ** | 89.9 µU/ml | 2.6-24.91 |
С-peptide | 1,41 ng/ml | 1.1–4.41 |
* kit Roche |
** kit Abbott |
1 - Reference interval for euglycemia |
According to the findings, FH was confirmed due to exogenous administration of an insulin analog preparation - Munchausen's syndrome. After discussing the results, the patient calmly denied the administration of insulin preparations. We had a serious conversation about the need to take medications only with doctor’s prescription and the potential danger to life and health of independent use.A psychiatrist consulted the patient and diagnosed the psychogenically induced chronic anxiety-depressive disorder with panic attacks. Found out that when she was 11 years old she suffered from severe criminal stress, tried to hold herself outwardly, gradually had anxiety attacks, which she relieved by smoking 2–3 packs a day, milder anxiety attacks by several cigarettes; 2017, she suffered a severe loss reaction, after which, in order to calm down, there were repeated alcoholic excesses. The patient was given recommendations for drug treatment and further psychotherapy.