With 60 units of insulin per day, the patient's glycation is still as high as 11.5%. What went wrong?

*For medical professionals only for reference Amenorrhea, hypothyroidism, diabetes, hyponatremia.
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What happened to this patient? The author recently encountered such a patient in clinical work
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 The case express patient, a 37-year-old young woman, was admitted to the hospital with the chief complaint of "fatigue for more than 5 days, aggravated with fever for 1 day"
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Five days before admission, the patient developed general malaise without obvious incentive, poor appetite, easy sweating, chest tightness and suffocation, and the rest were unremarkable
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Therefore, the patient did not pay attention and did not seek medical attention
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One day ago, the patient's symptoms of general weakness worsened than before.
He developed fever this morning, with a temperature of up to 39.
0°C.
He went to our hospital and was admitted to the hospital for systemic treatment
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Since the onset of the disease, the diet has been poor, the stools have been normal, the sleep has been poor, and the weight has not changed
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She had a history of type 2 diabetes for more than 6 years.
She was treated with insulin for 20u ih in the morning and evening, and her blood sugar was not well controlled
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Denied other medical history such as hypertension, coronary heart disease, cerebrovascular disease
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Personal history and history of menstruation, marriage and childbearing: 15 years old at menarche, with a history of amenorrhea for more than 10 years
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Menstruation came back 3 months ago, and the cycle is irregular
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Married at the right age, has 1 son, and the family is healthy
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No obvious abnormality was found in the family genetic history
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Physical examination: Young female, physical examination cooperation, no yellowing of skin and mucous membranes, no bleeding spots and rashes, thick skin, enlarged skull, hypertrophic lips, widened tooth spacing, and thick and hypertrophic limbs
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There was no enlargement of superficial lymph nodes in the whole body, and no obvious abnormality was found in the examination of heart, lung and abdomen
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The rest of the physical examination was unremarkable
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Check in outpatient clinic before admission: 2021-04-01 Blood analysis + high-sensitivity C-reactive protein + procalcitonin: neutrophil ratio 88.
1%↑, white blood cells 8.
5×109/L, C-reactive protein 159.
6 mg/L↑ , Procalcitonin 12.
00 ng/ml
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2021-04-01 Emergency biochemistry: alanine aminotransferase 14 U/L (0-35), aspartate aminotransferase 19 U/L (0-40), glucose 23.
36 mmol/L (3.
8-6.
1), urea nitrogen 7.
04 mmol/L (2.
86-8.
2), serum creatinine 79 ummol/L (44-97.
5), creatine kinase 69 U/L (38-174), creatine kinase isoenzyme 6 (0-24), blood amylase 17 U/ L(0-100)
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2021-04-01 Urine routine examination plus sediment: glucose +4 mmol/L↑, protein +3↑, urobilinogen +2↑, urinary occult blood +30 CELL/ul↑, ketone body +3↑, leukocyte 64.
70/ul ul↑, red blood cells 360.
80/ul↑, bacteria 8240.
50/ul↑, red blood cells (high power) 64.
9/HPF↑, white blood cells (high power) 11.
7/HPF↑
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2021-04-01 BNP<100 pg/ml (0-300); 2021-04-01 Arterial blood gas analysis pH 7.
414, sodium 126.
5 mmol/L, potassium 3.
61 mmol/L, PCO2 24.
5 mmHg, PO2 66.
3 mmHg, Glu23.
9 mmol/L
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2021-04-01 CT of chest + upper abdomen: bilateral pneumonia, fibrous foci (significant on the right side); obvious elevation of the right diaphragm, the cause is to be investigated; consistent with CT findings of subcutaneous edema; left kidney gas; gastric and intestinal effusion , gas accumulation; consider multiple retroperitoneal lymphadenopathy; intestinal gas and liquid flat shadow, please combine clinical exclusion of intestinal obstruction; abdominal enhanced scan is recommended
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After the initial treatment plan was admitted to the hospital, we carefully analyzed the patient's condition, and considered that the patient's stool was unobstructed, so intestinal obstruction was not considered.
Combined with the current examination results, the patient's diagnosis was considered: type 1.
2 diabetes, type 2 diabetic ketosis, type 2 diabetes mellitus Sexual nephropathy 2.
Pneumonia 3.
Urinary tract infection 4.
Hyponatremia 5.
Lower extremity edema was treated with antibiotics to control infection, massive fluid replacement to eliminate ketone bodies, insulin to regulate blood sugar, supplement electrolytes, and lower urine protein.
Complete relevant auxiliary inspections
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The next day after admission, some tests were reported: ion analysis: sodium 135.
7 mmol/L (136-145), potassium 3.
64 mmol/L, chloride 106.
1 mmol/L (96-108), calcium 1.
86 mmol/L L (2.
1-2.
8), magnesium ion 1.
02 mmol/L (0.
8-1.
3), phosphorus 0.
63 mmol/L (0.
96-2.
1); recheck liver function: serum total protein 45.
1 g/L (62-88), albumin 24.
8 g/L (35-54); Coagulation five items: D-dimer 1.
21 ng/ml (0-0.
5); Glycated hemoglobin: 11.
5% (3.
8-5.
8); Urine trace protein: 162 mg/L (0- 25); five items of thyroid function: free T3 0.
775 pmmol/l (3.
1-6.
8), free T4 7.
65 pmmol/l (12-22), thyrotropin 2.
19 uIU/mL (0.
27-4.
2), anti-thyroglobulin antibody Normal, anti-thyroid peroxidase antibody normal; thyroid color Doppler ultrasound: no obvious abnormality; three myocardial infarction, normal blood lipids
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After these test results came out, we added the diagnosis to the patient: hypoalbuminemia, hypocalcemia, hypophosphatemia, and hypothyroidism
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In the treatment, we have given supplemental protein and thyroid hormone therapy
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The case introduction is here, if you think the diagnosis is clear, it is hasty! In fact, there are still many unresolved problems in this patient
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Four major doubts in the diagnosis process Doubt 1: The first is the diagnosis of diabetes, is it as simple as type 2 diabetes? The patient has a history of diabetes for 6 years, that is, the onset of diabetes at the age of 31.
He was relatively young at the time of onset.
The glycated hemoglobin was 11.
5% this time, indicating that the patient's blood sugar control was very poor
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▌ Preliminary solution: We urgently need to classify patients with diabetes
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So the patient was checked for diabetes autoantibodies, fasting insulin and C-peptide
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The autoantibodies were negative, basically ruling out type 1 diabetes.
The fasting C-peptide was 2.
65 ng/ml (0.
69-2.
45) and the fasting insulin was 20.
32 uU/ml (1.
1-17.
0), suggesting hyperinsulinemia and acceptable pancreatic function
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However, we found another problem in the follow-up blood sugar control.
In the past, the patient used 40 units of insulin per day and the effect was still not good.
In our follow-up treatment, the dosage even reached 60 units, but it was still difficult to control.
Insulin resistance, the patient is neither type 1 diabetes, but also has insulin resistance.
Are there other causes? Doubt 2: Secondly, patients have different electrolyte imbalance problems, how to explain? The patient's hyponatremia is well explained, because the patient already has diabetic ketosis, coupled with poor eating, is very prone to hyponatremia
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So why does hypocalcemia and hypophosphatemia occur? ▌ Preliminary solution: We need to combine the albumin-corrected results for diagnosis
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After correction by albumin, the serum calcium value was 2.
164 mmol/L [corrected calcium concentration=serum calcium+0.
02*(40-albumin)], which was within the normal range
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Therefore, the adjusted results suggest that hypocalcemia should not be considered in this patient
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The common causes of hypophosphatemia are reduced intestinal absorption, increased renal excretion, and intracellular and intracellular redistribution.
Although it has been found that diabetic ketoacidosis can be complicated by hypophosphatemia, we are still trying to determine whether the patient is due to parathyroid glands.
Calcium and phosphorus metabolism disorders caused by hormones, so the patient was checked for parathyroid hormone
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The patient's parathyroid hormone was 25 pg/ml, which was within the normal range
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Therefore, the etiology of hypophosphatemia still needs to be searched
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 Doubt 3: The patient still has severe hypoalbuminemia, how to explain it? Common causes of hypoproteinemia: 1.
Insufficient protein intake or malabsorption 2.
Impaired protein synthesis, more common in liver damage caused by various causes 3.
Long-term loss of large amounts of protein Patients with malignant tumors and endocrine diseases
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▌ Preliminary solution: Although this patient has poor eating, it cannot be fully explained.
The etiology of hypoalbuminemia is still unclear, and further observation is required
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 Doubt 4: The patient had amenorrhea 10 years ago.
Is it primary amenorrhea or secondary amenorrhea? Moreover, the patient also showed signs of decreased thyroid function 10 years ago, but this time, the patient's thyroid color Doppler ultrasound and thyroid-stimulating hormone showed no obvious abnormality.
Why? ▌ Preliminary solution: For this reason, we first checked the gynecological color Doppler ultrasound for the patient
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Tip: Myometrium strip strong echo
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From this point of view, it is not in line with primary amenorrhea
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We continued to check six sex hormones for the patient
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Prolactin 12.
20 ng/ml (4.
1-28.
9), estradiol 83 pg/ml, follicle-stimulating hormone <1 mIU/ml, luteinizing hormone <0.
2 mIU/ml, progesterone 0.
22 ng/ml, testosterone 19.
16 ng /dl (9.
81-82.
1)
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The results of the six items of sex hormones suggested that there was a problem with the function of the patient's pituitary gland to secrete gonadotropins.
Combined with the results of the five items of the patient's thyroid function, it further suggested that the patient's thyroid axis and upstream of the gonadal axis had problems
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The patients have many problems that have not been resolved, and our thoughts are confused in the process of sorting out
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I remember that a teacher once taught us to try to explain all the symptoms, abnormal signs and auxiliary examinations of patients with one disease, that is, the method of "monism"
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Is there a hidden cause behind all the clinical symptoms of this patient? In-depth investigation.
We just mentioned that patients with hypothyroidism and amenorrhea have prompted us to have problems upstream of the endocrine axis, which all point to the problem of the hypothalamus or pituitary gland
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Combined with the patient's physical examination, we made an appointment for the patient's cranial magnetic resonance examination
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Immediately, MRI results reported abnormal signal in the patient's sella as well as skull thickening and possible metabolic bone disease
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Based on the clinical manifestations of the patient, we highly suspect that the patient has acromegaly caused by pituitary tumor.
The patient’s blood sugar is difficult to control, and it is also related to the release of growth hormone from the pituitary tumor.
Since pituitary tumor surgery is temporarily unavailable in our hospital, we recommend that the patient go to a superior The hospital continues to treat
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 Figure 1 Magnetic resonance imaging of the patient's brain About 2 months later, we returned to the patient
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After the patient was hospitalized in a higher-level hospital, the growth hormone and insulin-like growth factor-1 (908.
40 ng/ml) were checked immediately, and the results were also elevated, basically confirming the pituitary growth hormone tumor.
After strict preoperative evaluation , eventually given pituitary tumor surgery
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At present, the recovery is good.
Although menstruation has not fully recovered, blood sugar has been significantly easier to control than before.
The total daily insulin has been reduced to 20U, and there are no other obvious symptoms of discomfort
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Looking back at this case, at first all the clinical symptoms were somewhat fragmented, and it seemed that there was no obvious connection between them, but after careful analysis, it seemed that it could be explained by pituitary tumors
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 The cause of the patient's diabetes may be that the pituitary tumor releases a large amount of growth hormone and insulin-like growth factor-1, which leads to the decline of glucose tolerance, and then develops into diabetes with the decline of pancreatic function; this time, ketoacidic acid was secondary to the infection.
Poisoning, the problem of severe insulin resistance in patients is also due to excessive release of growth hormone; hypothyroidism and amenorrhea are due to pituitary aneurysm leading to hypofunction of the anterior pituitary gland, resulting in limited release of hormones; hypophosphatemia It is also due to the increase in bone turnover caused by growth hormone and insulin-like growth factor-1, which leads to abnormal calcium and phosphorus metabolism; finally, hypoalbuminemia.
As mentioned above, the etiology of hypoalbuminemia is multi-faceted.
Through consulting the data, it is found that although it has no direct relationship with pituitary tumors, it is obviously related to the imbalance of endocrine hormones induced by pituitary tumors
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The author believes that, first, it may be related to the poor eating of patients after ketoacidosis, resulting in malnutrition hypoalbuminemia; second, hypothyroidism will also affect the synthesis of albumin, causing hypoproteinemia
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What difficult but beneficial cases have you encountered in clinical practice? Come and share with us in the comment section! References: [1] Liu Shumei, Zhou Xiumei.
Analysis of thyroid function in elderly patients with hypoalbuminemia [J].
Journal of Hebei Medical University, 2010,31(5):595-596.
DOI:10.
3969/j.
issn.
1007- 3205.
2010.
05.
039.